Genetic Testing in Guiding Treatment for Patients With Brain Metastases

Genomically-Guided Treatment Trial in Brain Metastases

This phase II trial studies how well genetic testing works in guiding treatment for patients with solid tumors that have spread to the brain. Several genes have been found to be altered or mutated in brain metastases such as NTRK, ROS1, CDK, PI3K, or KRAS G12C. Medications that target these genes such as abemaciclib, paxalisib, entrectinib and adagrasib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Genetic testing may help doctors tailor treatment for each mutation.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Malignant Solid Neoplasm; Metastatic Malignant Neoplasm in the Brain; NTRK Family Gene Mutation; CDK Gene Mutation; PI3K Gene Mutation; ROS1 Gene Mutation; KRAS G12C Mutation
• Intervention / Treatment: Drug: Abemaciclib; Drug: Entrectinib; Drug: PI3K Inhibitor paxalisib; Drug: Adagrasib

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the activity of a CDK inhibitor in patients with progressive brain metastases derived from lung cancer, breast cancer, and other cancers harboring actionable genetic alterations associated with sensitivity to CDK inhibitors as measured by response rate (Response Assessment in Neuro-Oncology [RANO] criteria).

II. To determine the activity of a PI3K inhibitor in patients with progressive brain metastases derived from lung cancer, breast cancer, and other cancers harboring actionable genetic alterations in the PI3K pathway as measured by response rate (RANO criteria).

III: To determine the activity of an NTRK/ROS1 inhibitor in patients with progressive brain metastases derived from lung cancer harboring actionable NTRK/ROS1 gene fusions as measured by response rate (RANO criteria).

IV. To determine the activity of an KRAS G12C inhibitor in patients with progressive brain metastases derived from lung cancer, and other cancers harboring a KRAS G12C mutation as measured by response rate (RANO criteria).

SECONDARY OBJECTIVES:

I. To evaluate the systemic response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in each of the cohorts determined by treatment and primary cancer type.

II. To evaluate the clinical benefit rate (complete response [CR] + partial response [PR] + stable disease [SD]) by Brain Metastases (BM)-RANO for central nervous system (CNS) in each of the cohorts determined by treatment and primary cancer type.

III. To evaluate the clinical benefit rate (CR + PR + SD) by RECIST for extracranial disease in each of the cohorts determined by treatment and primary cancer type.

IV. To evaluate the duration of response by BM-RANO in each of the cohorts determined by treatment and primary cancer type.

V. To evaluate the duration of response by RECIST in each of the cohorts determined by treatment and primary cancer type.

VI. To evaluate the progression-free survival for intracranial disease in each of the cohorts determined by treatment and primary cancer type.

VII. To evaluate the progression-free survival for extracranial disease in each of the cohorts determined by treatment and primary cancer type.

VIII. To evaluate the site of first progression (CNS versus [vs] non-CNS) in each of the cohorts determined by treatment and primary cancer type.

IX. To evaluate the overall survival in each of the cohorts determined by treatment and primary cancer type.

X. To evaluate the toxicity profile of agents in patients with brain metastases in each of the cohorts determined by treatment and primary cancer type.

OUTLINE: Patients are assigned to 1 of 4 arms.

ARM I (CDK GENE MUTATION): Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II (PI3K GENE MUTATION): Patients receive PI3K inhibitor paxalisib PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM III (NTRK/ROS1 GENE MUTATION): Patients receive entrectinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM IV (KRAS G12C MUTATION): Patients receive adagrasib (MRTX849) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 8 weeks for 2 years, then every 3 months for years 3-4, and then every 6 months thereafter for up to 5 years after registration.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 98508
      • Anchorage Associates in Radiation Medicine
    • Anchorage, Alaska, United States, 99508
      • Alaska Breast Care and Surgery LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care
    • Anchorage, Alaska, United States, 99508
      • Anchorage Oncology Centre
    • Anchorage, Alaska, United States, 99508
      • Katmai Oncology Group
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
    • Anchorage, Alaska, United States, 99504
      • Anchorage Radiation Therapy Center
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital in Arizona
    • Phoenix, Arizona, United States, 85004
      • Cancer Center at Saint Joseph's
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Arkansas
    • Fort Smith, Arkansas, United States, 72903
      • Mercy Hospital Fort Smith
    • Hot Springs, Arkansas, United States, 71913
      • CHI Saint Vincent Cancer Center Hot Springs
  • California
    • Arroyo Grande, California, United States, 93420
      • Mission Hope Medical Oncology - Arroyo Grande
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Dublin, California, United States, 94568
      • Epic Care-Dublin
    • Emeryville, California, United States, 94608
      • Bay Area Breast Surgeons Inc
    • Emeryville, California, United States, 94608
      • Epic Care Partners in Cancer Care
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • Bay Area Tumor Institute
    • Orange, California, United States, 92868
      • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • San Diego, California, United States, 92123
      • Sharp Memorial Hospital
    • San Luis Obispo, California, United States, 93401
      • Pacific Central Coast Health Center-San Luis Obispo
    • Santa Maria, California, United States, 93444
      • Mission Hope Medical Oncology - Santa Maria
    • Torrance, California, United States, 90509
      • Torrance Memorial Medical Center
    • Torrance, California, United States, 90505
      • Torrance Memorial Physician Network - Cancer Care
    • Walnut Creek, California, United States, 94597
      • Epic Care Cyberknife Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80907
      • Rocky Mountain Cancer Centers-Penrose
    • Denver, Colorado, United States, 80210
      • AdventHealth Porter
    • Durango, Colorado, United States, 81301
      • Mercy Medical Center
    • Durango, Colorado, United States, 81301
      • CommonSpirit Cancer Center Mercy
    • Lakewood, Colorado, United States, 80228
      • Saint Anthony Hospital
    • Littleton, Colorado, United States, 80122
      • AdventHealth Littleton
    • Longmont, Colorado, United States, 80501
      • Longmont United Hospital
    • Longmont, Colorado, United States, 80501
      • Rocky Mountain Cancer Centers-Longmont
    • Parker, Colorado, United States, 80138
      • AdventHealth Parker
    • Pueblo, Colorado, United States, 81004
      • Saint Mary Corwin Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Center/Yale-New Haven Hospital
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Boca Raton Regional Hospital
    • Coral Gables, Florida, United States, 33146
      • UM Sylvester Comprehensive Cancer Center at Coral Gables
    • Deerfield Beach, Florida, United States, 33442
      • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital Midtown
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Atlanta, Georgia, United States, 30342
      • Emory Saint Joseph's Hospital
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Cancer Care Center-Caldwell
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Health - Coeur d'Alene
    • Emmett, Idaho, United States, 83617
      • Walter Knox Memorial Hospital
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Cancer Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute-Meridian
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Cancer Institute - Meridian
    • Nampa, Idaho, United States, 83687
      • Saint Alphonsus Cancer Care Center-Nampa
    • Nampa, Idaho, United States, 83687
      • Saint Luke's Cancer Institute - Nampa
    • Post Falls, Idaho, United States, 83854
      • Kootenai Clinic Cancer Services - Post Falls
    • Sandpoint, Idaho, United States, 83864
      • Kootenai Clinic Cancer Services - Sandpoint
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Cancer Institute - Twin Falls
  • Illinois
    • Alton, Illinois, United States, 62002
      • OSF Saint Anthony's Health Center
    • Aurora, Illinois, United States, 60504
      • Rush-Copley Medical Center
    • Barrington, Illinois, United States, 60010
      • Advocate Good Shepherd Hospital
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60657
      • Advocate Illinois Masonic Medical Center
    • Chicago, Illinois, United States, 60612
      • Rush MD Anderson Cancer Center
    • Crystal Lake, Illinois, United States, 60014
      • AMG Crystal Lake - Oncology
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • DeKalb, Illinois, United States, 60115
      • Northwestern Medicine Cancer Center Kishwaukee
    • Downers Grove, Illinois, United States, 60515
      • Advocate Good Samaritan Hospital
    • Effingham, Illinois, United States, 62401
      • Carle Physician Group-Effingham
    • Elgin, Illinois, United States, 60123
      • Advocate Sherman Hospital
    • Geneva, Illinois, United States, 60134
      • Northwestern Medicine Cancer Center Delnor
    • Hazel Crest, Illinois, United States, 60429
      • Advocate South Suburban Hospital
    • Lake Forest, Illinois, United States, 60045
      • Northwestern Medicine Lake Forest Hospital
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • Mount Vernon, Illinois, United States, 62864
      • SSM Health Good Samaritan
    • Oak Lawn, Illinois, United States, 60453-2699
      • Advocate Christ Medical Center
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
    • Urbana, Illinois, United States, 61801
      • The Carle Foundation Hospital
    • Warrenville, Illinois, United States, 60555
      • Northwestern Medicine Cancer Center Warrenville
    • Yorkville, Illinois, United States, 60560
      • Rush-Copley Healthcare Center
  • Iowa
    • Ames, Iowa, United States, 50010
      • Mary Greeley Medical Center
    • Ames, Iowa, United States, 50010
      • McFarland Clinic - Ames
    • Ankeny, Iowa, United States, 50023
      • UI Health Care Mission Cancer and Blood - Ankeny Clinic
    • Boone, Iowa, United States, 50036
      • McFarland Clinic - Boone
    • Carroll, Iowa, United States, 51401
      • Saint Anthony Regional Hospital
    • Clive, Iowa, United States, 50325
      • Mercy Cancer Center-West Lakes
    • Clive, Iowa, United States, 50325
      • UI Health Care Mission Cancer and Blood - West Des Moines Clinic
    • Council Bluffs, Iowa, United States, 51503
      • Alegent Health Mercy Hospital
    • Creston, Iowa, United States, 50801
      • Greater Regional Medical Center
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50314
      • Broadlawns Medical Center
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50309
      • UI Health Care Mission Cancer and Blood - Des Moines Clinic
    • Des Moines, Iowa, United States, 50314
      • UI Health Care Mission Cancer and Blood - Laurel Clinic
    • Fort Dodge, Iowa, United States, 50501
      • McFarland Clinic - Trinity Cancer Center
    • Fort Dodge, Iowa, United States, 50501
      • UI Healthcare Mission Cancer and Blood - Fort Dodge
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Jefferson, Iowa, United States, 50129
      • McFarland Clinic - Jefferson
    • Marshalltown, Iowa, United States, 50158
      • McFarland Clinic - Marshalltown
    • Waukee, Iowa, United States, 50263
      • UI Health Care Mission Cancer and Blood - Waukee Clinic
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
    • West Des Moines, Iowa, United States, 50266
      • Mercy Medical Center-West Lakes
  • Kansas
    • Garden City, Kansas, United States, 67846
      • Central Care Cancer Center - Garden City
    • Great Bend, Kansas, United States, 67530
      • Central Care Cancer Center - Great Bend
    • Hays, Kansas, United States, 67601
      • HaysMed
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Olathe, Kansas, United States, 66061
      • The University of Kansas Cancer Center - Olathe
    • Overland Park, Kansas, United States, 66210
      • University of Kansas Cancer Center-Overland Park
    • Overland Park, Kansas, United States, 66211
      • University of Kansas Hospital-Indian Creek Campus
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital-Westwood Cancer Center
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Flaget Memorial Hospital
    • Corbin, Kentucky, United States, 40701
      • Commonwealth Cancer Center-Corbin
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
    • Lexington, Kentucky, United States, 40504
      • Saint Joseph Radiation Oncology Resource Center
    • Lexington, Kentucky, United States, 40509
      • Saint Joseph Hospital East
    • London, Kentucky, United States, 40741
      • Saint Joseph London
    • Louisville, Kentucky, United States, 40202
      • Jewish Hospital
    • Louisville, Kentucky, United States, 40245
      • UofL Health Medical Center Northeast
    • Louisville, Kentucky, United States, 40215
      • Saints Mary and Elizabeth Hospital
    • Shepherdsville, Kentucky, United States, 40165
      • Jewish Hospital Medical Center South
  • Louisiana
    • Monroe, Louisiana, United States, 71202
      • Ochsner LSU Health Monroe Medical Center
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
    • New Orleans, Louisiana, United States, 70112
      • University Medical Center New Orleans
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Science Center
    • Shreveport, Louisiana, United States, 71103
      • LSU Health Sciences Center at Shreveport
    • Shreveport, Louisiana, United States, 71101
      • Ochsner LSU Health Saint Mary's Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Springfield, Massachusetts, United States, 01104
      • Mercy Medical Center
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center - University Campus
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Rogel Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Brighton, Michigan, United States, 48114
      • Trinity Health IHA Medical Group Hematology Oncology - Brighton
    • Brighton, Michigan, United States, 48116
      • University of Michigan - Brighton Center for Specialty Care
    • Brighton, Michigan, United States, 48114
      • Trinity Health Medical Center - Brighton
    • Brownstown, Michigan, United States, 48183
      • Henry Ford Cancer Institute-Downriver
    • Canton, Michigan, United States, 48188
      • Trinity Health IHA Medical Group Hematology Oncology - Canton
    • Canton, Michigan, United States, 48188
      • Trinity Health Medical Center - Canton
    • Caro, Michigan, United States, 48723
      • Caro Cancer Center
    • Chelsea, Michigan, United States, 48118
      • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
    • Chelsea, Michigan, United States, 48118
      • Chelsea Hospital
    • Clarkston, Michigan, United States, 48346
      • Hematology Oncology Consultants-Clarkston
    • Clarkston, Michigan, United States, 48346
      • Newland Medical Associates-Clarkston
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital-Clinton Township
    • Dearborn, Michigan, United States, 48126
      • Henry Ford Medical Center-Fairlane
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Detroit, Michigan, United States, 48236
      • Henry Ford Health Saint John Hospital
    • East China Township, Michigan, United States, 48054
      • Henry Ford River District Hospital
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesee Hematology Oncology PC
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Flint, Michigan, United States, 48503
      • Cancer Hematology Centers - Flint
    • Grand Rapids, Michigan, United States, 49503
      • Trinity Health Grand Rapids Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Corewell Health Grand Rapids Hospitals - Butterworth Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Henry Ford Saint John Hospital - Academic
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Henry Ford Saint John Hospital - Breast
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Henry Ford Saint John Hospital - Van Elslander
    • Jackson, Michigan, United States, 49201
      • Allegiance Health
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49009
      • Beacon Kalamazoo Cancer Center
    • Kalamazoo, Michigan, United States, 49048
      • Beacon Kalamazoo
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Livonia, Michigan, United States, 48154
      • Hope Cancer Clinic
    • Macomb, Michigan, United States, 48044
      • Henry Ford Warren Hospital - Breast Macomb
    • Macomb, Michigan, United States, 48044
      • Henry Ford Saint John Hospital - Macomb Medical
    • Marlette, Michigan, United States, 48453
      • Saint Mary's Oncology/Hematology Associates of Marlette
    • Monroe, Michigan, United States, 48162
      • Toledo Clinic Cancer Centers-Monroe
    • Muskegon, Michigan, United States, 49444
      • Trinity Health Muskegon Hospital
    • Niles, Michigan, United States, 49120
      • Corewell Health Lakeland Hospitals - Niles Hospital
    • Norton Shores, Michigan, United States, 49444
      • Cancer and Hematology Centers of Western Michigan - Norton Shores
    • Novi, Michigan, United States, 48377
      • Henry Ford Medical Center-Columbus
    • Novi, Michigan, United States, 48374
      • Henry Ford Health Providence Novi Hospital
    • Pontiac, Michigan, United States, 48341
      • Hope Cancer Center
    • Pontiac, Michigan, United States, 48341
      • Newland Medical Associates-Pontiac
    • Pontiac, Michigan, United States, 48341
      • Trinity Health Saint Joseph Mercy Oakland Hospital
    • Pontiac, Michigan, United States, 48341
      • Michigan Healthcare Professionals Pontiac
    • Reed City, Michigan, United States, 49677
      • Corewell Health Reed City Hospital
    • Rochester Hills, Michigan, United States, 48309
      • Henry Ford Rochester Hospital
    • Saginaw, Michigan, United States, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • Saginaw, Michigan, United States, 48601
      • MyMichigan Medical Center Saginaw
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Saint Joseph Hospital
    • Shelby, Michigan, United States, 48315
      • Henry Ford Macomb Health Center - Shelby Township
    • Southfield, Michigan, United States, 48075
      • Henry Ford Health Providence Southfield Hospital
    • Sterling Heights, Michigan, United States, 48312
      • Bhadresh Nayak MD PC-Sterling Heights
    • Tawas City, Michigan, United States, 48764
      • MyMichigan Medical Center Tawas
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48088
      • Advanced Breast Care Center PLLC
    • Warren, Michigan, United States, 48093
      • Macomb Hematology Oncology PC
    • Warren, Michigan, United States, 48093
      • Henry Ford Madison Heights Hospital - Breast
    • Warren, Michigan, United States, 48093
      • Henry Ford Health Warren Hospital
    • Warren, Michigan, United States, 48093
      • Henry Ford Warren Hospital - GLCMS
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford West Bloomfield Hospital
    • West Branch, Michigan, United States, 48661
      • Saint Mary's Oncology/Hematology Associates of West Branch
    • Wyoming, Michigan, United States, 49519
      • University of Michigan Health - West
    • Ypsilanti, Michigan, United States, 48197
      • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Ypsilanti, Michigan, United States, 48106
      • Huron Gastroenterology PC
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Burnsville, Minnesota, United States, 55337
      • Minnesota Oncology - Burnsville
    • Cambridge, Minnesota, United States, 55008
      • Cambridge Medical Center
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maple Grove, Minnesota, United States, 55369
      • Fairview Clinics and Surgery Center Maple Grove
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55454
      • Health Partners Inc
    • Monticello, Minnesota, United States, 55362
      • Monticello Cancer Center
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Princeton, Minnesota, United States, 55371
      • Fairview Northland Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center at Saint Cloud Hospital
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
    • Wyoming, Minnesota, United States, 55092
      • Fairview Lakes Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Ballwin, Missouri, United States, 63011
      • Mercy Oncology and Hematology - Clayton-Clarkson
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Branson, Missouri, United States, 65616
      • Cox Cancer Center Branson
    • City of Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Columbia, Missouri, United States, 65212
      • MU Health - University Hospital/Ellis Fischel Cancer Center
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital Joplin
    • Kansas City, Missouri, United States, 64154
      • University of Kansas Cancer Center - North
    • Lee's Summit, Missouri, United States, 64064
      • University of Kansas Cancer Center - Lee's Summit
    • North Kansas City, Missouri, United States, 64116
      • University of Kansas Cancer Center at North Kansas City Hospital
    • Rolla, Missouri, United States, 65401
      • Mercy Clinic-Rolla-Cancer and Hematology
    • Rolla, Missouri, United States, 65401
      • Phelps Health Delbert Day Cancer Institute
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • St Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • St Louis, Missouri, United States, 63136
      • Siteman Cancer Center at Christian Hospital
    • St Louis, Missouri, United States, 63109
      • Mercy Infusion Center - Chippewa
    • St Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • St Louis, Missouri, United States, 63128
      • Mercy Hospital South
    • Washington, Missouri, United States, 63090
      • Mercy Hospital Washington
  • Montana
    • Anaconda, Montana, United States, 59711
      • Community Hospital of Anaconda
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Health Deaconess Hospital
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Sletten Cancer Institute
    • Kalispell, Montana, United States, 59901
      • Logan Health Medical Center
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
    • Missoula, Montana, United States, 59804
      • Community Medical Center
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Nebraska Cancer Specialists/Oncology Hematology West PC
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
    • Lincoln, Nebraska, United States, 68510
      • Saint Elizabeth Regional Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Omaha, Nebraska, United States, 68130
      • Alegent Health Lakeside Hospital
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Papillion, Nebraska, United States, 68046
      • Midlands Community Hospital
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
    • Neptune City, New Jersey, United States, 07753
      • Jersey Shore Medical Center
    • Pennington, New Jersey, United States, 08534
      • Capital Health Medical Center-Hopewell
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Lovelace Medical Center-Saint Joseph Square
    • Albuquerque, New Mexico, United States, 87109
      • Lovelace Radiation Oncology
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
  • New York
    • Brooklyn, New York, United States, 11215
      • New York-Presbyterian/Brooklyn Methodist Hospital
    • Elmira, New York, United States, 14905
      • Arnot Ogden Medical Center/Falck Cancer Center
    • Glens Falls, New York, United States, 12801
      • Glens Falls Hospital
    • Lake Success, New York, United States, 11042
      • Northwell Health/Center for Advanced Medicine
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
    • New York, New York, United States, 10016
      • Laura and Isaac Perlmutter Cancer Center at NYU Langone
    • New York, New York, United States, 10075
      • Lenox Hill Hospital
    • New York, New York, United States, 10065
      • Manhattan Eye Ear and Throat Hospital
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
    • Verona, New York, United States, 13478
      • Upstate Cancer Center at Verona
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center/Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28210
      • Atrium Health Pineville/LCI-Pineville
    • Concord, North Carolina, United States, 28025
      • Atrium Health Cabarrus/LCI-Concord
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Hendersonville, North Carolina, United States, 28791
      • Margaret R Pardee Memorial Hospital
    • Kenansville, North Carolina, United States, 28349
      • ECU Health Oncology Kenansville
    • Kinston, North Carolina, United States, 28501
      • ECU Health Oncology Kinston
    • Richlands, North Carolina, United States, 28574
      • ECU Health Oncology Richlands
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Centerville, Ohio, United States, 45459
      • Miami Valley Hospital South
    • Chardon, Ohio, United States, 44024
      • Geauga Hospital
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Center-UC Medical Center
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital - Cincinnati
    • Cincinnati, Ohio, United States, 45242
      • Bethesda North Hospital
    • Cincinnati, Ohio, United States, 45247
      • TriHealth Cancer Institute-Westside
    • Cincinnati, Ohio, United States, 45255
      • TriHealth Cancer Institute-Anderson
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43214
      • Columbus Oncology and Hematology Associates Inc
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Dayton, Ohio, United States, 45409
      • Premier Blood and Cancer Center
    • Delaware, Ohio, United States, 43015
      • Delaware Health Center-Grady Cancer Center
    • Delaware, Ohio, United States, 43015
      • Grady Memorial Hospital
    • Dublin, Ohio, United States, 43016
      • Dublin Methodist Hospital
    • Dublin, Ohio, United States, 43016
      • Columbus Oncology and Hematology Associates
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Miami Valley Cancer Care and Infusion
    • Mansfield, Ohio, United States, 44903
      • OhioHealth Mansfield Hospital
    • Marion, Ohio, United States, 43302
      • OhioHealth Marion General Hospital
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
    • Middleburg Heights, Ohio, United States, 44130
      • UH Seidman Cancer Center at Southwest General Hospital
    • Parma, Ohio, United States, 44129
      • University Hospitals Parma Medical Center
    • Perrysburg, Ohio, United States, 43551
      • Mercy Health - Perrysburg Hospital
    • Ravenna, Ohio, United States, 44266
      • University Hospitals Portage Medical Center
    • Sandusky, Ohio, United States, 44870
      • UH Seidman Cancer Center at Firelands Regional Medical Center
    • Toledo, Ohio, United States, 43623
      • Mercy Health - Saint Anne Hospital
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic Cancer Centers-Toledo
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Wadsworth, Ohio, United States, 44281
      • University Hospitals Sharon Health Center
    • West Chester, Ohio, United States, 45069
      • University of Cincinnati Cancer Center-West Chester
    • Westlake, Ohio, United States, 44145
      • UH Seidman Cancer Center at Saint John Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Hospital Oklahoma City
  • Oregon
    • Baker City, Oregon, United States, 97814
      • Saint Alphonsus Cancer Care Center-Baker City
    • Bend, Oregon, United States, 97701
      • Saint Charles Health System
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Clackamas, Oregon, United States, 97015
      • Providence Cancer Institute Clackamas Clinic
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Ontario, Oregon, United States, 97914
      • Saint Alphonsus Cancer Care Center-Ontario
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Redmond, Oregon, United States, 97756
      • Saint Charles Health System-Redmond
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Allentown, Pennsylvania, United States, 18104
      • Saint Luke's Cancer Center - Allentown
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • Bethlehem, Pennsylvania, United States, 18015
      • Saint Luke's University Hospital-Bethlehem Campus
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Pocono Medical Center
    • Easton, Pennsylvania, United States, 18045
      • Saint Luke's Hospital-Anderson Campus
    • Hazleton, Pennsylvania, United States, 18201
      • Lehigh Valley Hospital-Hazleton
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Pennsylvania Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-Magee Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Quakertown, Pennsylvania, United States, 18951
      • Saint Luke's Hospital-Quakertown Campus
  • Texas
    • Bryan, Texas, United States, 77802
      • Saint Joseph Regional Cancer Center
    • Dallas, Texas, United States, 75235
      • Parkland Memorial Hospital
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
    • Fort Worth, Texas, United States, 76104
      • UT Southwestern/Simmons Cancer Center-Fort Worth
    • Houston, Texas, United States, 77030
      • Memorial Hermann Texas Medical Center
    • Humble, Texas, United States, 77338
      • Memorial Hermann Northeast Hospital
    • The Woodlands, Texas, United States, 77380
      • Memorial Hermann The Woodlands Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Vermont
    • Berlin Corners, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
    • Burlington, Vermont, United States, 05405
      • University of Vermont and State Agricultural College
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
    • Fairfax, Virginia, United States, 22033
      • Inova Fair Oaks Hospital
    • Midlothian, Virginia, United States, 23114
      • Bon Secours Saint Francis Medical Center
    • Richmond, Virginia, United States, 23230
      • Bon Secours Cancer Institute at Reynolds Crossing
  • Washington
    • Aberdeen, Washington, United States, 98520
      • Providence Regional Cancer System-Aberdeen
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Burien, Washington, United States, 98166
      • Highline Medical Center-Main Campus
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Edmonds, Washington, United States, 98026
      • Swedish Cancer Institute-Edmonds
    • Enumclaw, Washington, United States, 98022
      • Saint Elizabeth Hospital
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Federal Way, Washington, United States, 98003
      • Saint Francis Hospital
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Lacey, Washington, United States, 98503
      • Providence Regional Cancer System-Lacey
    • Lakewood, Washington, United States, 98499
      • Saint Clare Hospital
    • Longview, Washington, United States, 98632
      • PeaceHealth Saint John Medical Center
    • Poulsbo, Washington, United States, 98370
      • Harrison HealthPartners Hematology and Oncology-Poulsbo
    • Seattle, Washington, United States, 98107
      • Swedish Medical Center-Ballard Campus
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98122-5711
      • Swedish Medical Center-Cherry Hill
    • Sedro-Woolley, Washington, United States, 98284
      • PeaceHealth United General Medical Center
    • Shelton, Washington, United States, 98584
      • Providence Regional Cancer System-Shelton
    • Silverdale, Washington, United States, 98383
      • Saint Michael Cancer Center
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties PLLC
    • Tacoma, Washington, United States, 98405
      • Franciscan Research Center-Northwest Medical Plaza
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Yelm, Washington, United States, 98597
      • Providence Regional Cancer System-Yelm
  • Wisconsin
    • Burlington, Wisconsin, United States, 53105
      • Aurora Cancer Care-Southern Lakes VLCC
    • Cudahy, Wisconsin, United States, 53110
      • Aurora Saint Luke's South Shore
    • Germantown, Wisconsin, United States, 53022
      • Aurora Health Care Germantown Health Center
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • Marinette, Wisconsin, United States, 54143
      • Aurora Bay Area Medical Group-Marinette
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Aurora Cancer Care-Milwaukee
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53233
      • Aurora Sinai Medical Center
    • Mukwonago, Wisconsin, United States, 53149
      • ProHealth D N Greenwald Center
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Oconomowoc, Wisconsin, United States, 53066
      • ProHealth Oconomowoc Memorial Hospital
    • Oshkosh, Wisconsin, United States, 54904
      • Vince Lombardi Cancer Clinic - Oshkosh
    • Racine, Wisconsin, United States, 53406
      • Aurora Cancer Care-Racine
    • Sheboygan, Wisconsin, United States, 53081
      • Vince Lombardi Cancer Clinic-Sheboygan
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • Waukesha, Wisconsin, United States, 53188
      • UW Cancer Center at ProHealth Care
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center
  • Wyoming
    • Cody, Wyoming, United States, 82414
      • Billings Clinic-Cody
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

PRE-REGISTRATION ELIGIBILITY CRITERIA (ALL PATIENTS) • Tissue available for biomarker testing (any brain metastasis tissue and extracranial site from any prior resection or biopsy).

REGISTRATION ELIGIBILITY CRITERIA (ALL PATIENTS)

• Participants must have histologically confirmed parenchymal metastatic disease to the brain from any solid tumor. Note: this includes patients that have controlled extracranial disease with progressive intracranial metastasis, as well as patients that have progressive intracranial and extracranial disease.

• New or progressive brain metastases are defined as any one of the following:

  • Untreated measurable lesions in patients who have received surgery and/or stereotactic radiosurgery (SRS) to one or more other lesions.
  • Progressive measurable lesions after radiation, surgery, or prior systemic therapy
  • Residual or progressive lesions after surgery if asymptomatic.
  • Patients who have had prior whole-brain radiotherapy (WBRT) and/or SRS and then whose lesions have progressed by BM-RANO criteria or there are new lesions, are eligible. Lesions treated with SRS may be eligible if there is unequivocal evidence of progression. For patients with NTRK or ROS1 mutations, entrectinib may be used for newly diagnosed brain metastases. Similarly, for patients with KRAS G12C mutations, MRTX849 may be used for newly diagnosed brain metastases.
  • Patients who have not previously been treated with cranial radiation (e.g. WBRT or SRS) are eligible, but such patients must be asymptomatic or neurologically stable from their CNS metastases.
• Measurable CNS disease (=> 10 mm).
• Ability to obtain magnetic resonance imaging (MRI)s with contrast
• No surgery within 2 weeks prior to or after registration.

• No chemotherapy within 14 days prior to registration (Note: for abemaciclib arm, a 21-day chemotherapy washout is required).

  • For melanoma, patients must have progressed after prior immune checkpoint blockade or for BRAF positive melanoma, BRAF/MEK inhibitors.
  • For lung cancer, EGFR mutant patients must have failed EGFR therapies
  • For HER2-positive breast cancer patients (regardless of ER/PR status), patients must have received at least one prior HER-2 directed therapy in the metastatic setting.
  • For triple negative breast cancer (TNBC), patients must have received at least one chemotherapy in the metastatic setting.
  • For estrogen receptor (ER) and/or progesterone receptor (PR)+ HER2-negative breast cancer, patients must have received at least one endocrine therapy in the metastatic setting.
  • Patients who have received prior treatment with any of the targeted treatments on this study are not eligible for that specific treatment arm(s), but could be eligible for other arms (e.g., a patient who has had prior treatment with abemaciclib would not be eligible for the abemaciclib arm, but could be eligible for another arm).
• Presence of clinically actionable alteration in NTRK, ROS1, KRAS G12C or CDK pathway or PI3K pathway in both a brain metastasis and extracranial site per central review.
• Not pregnant and not nursing, because this study involves investigational agents whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 14 days prior to registration is required (Note: for abemaciclib arm, pregnancy test is required =< 7 days prior to registration).
• No known current diffuse leptomeningeal involvement for the CDK, PI3K and NTRK arms (diffuse defined as leptomeningeal involvement throughout the CNS axis).Patients with focal leptomeningeal disease, with or without documented positive CSF cytology, are eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Adequate organ function.
• Absolute neutrophil count (ANC) >= 1,500/mm^3.
• Platelet count >= 100,000/mm^3.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) except in patients with Gilbert's disease. Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN).
• Creatinine =< 1.5 mg/dL OR calculated (Calc.) creatinine clearance > 45 mL/min except for patients in the adagrasib (MRTX849) (KRAS G12C) arm. For this arm, patients must have creatinine clearance ≥60 mL/min or glomerular filtration rate ≥60 mL/min/1.73m2 calculated using a validated prediction equation (e.g., Cockcroft-Gault, MDRD, or 24-hour urine CrCl).
• No uncontrolled medical comorbidities per investigator discretion (e.g. interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)
• Radiation to symptomatic non-target sites within neural axis is allowed prior to registration without washout (provided there is at least one untreated target lesion for measurement on study and radiation is completed prior to registration).
• Concurrent systemic corticosteroids are allowed if stable dose of dexamethasone for 7 days prior to registration. Baseline doses and changes in steroid dosing will be captured.
• No concurrent administration of anticancer therapies (except for endocrine therapy or continuation of hormonal therapy or trastuzumab in breast cancer patients for the PI3K and CDK inhibitor arms). . No chemotherapy, targeted therapy or immunotherapy within 14 days prior to entering the study (Note: For abemaciclib arm, a 21-day chemotherapy washout is required).
• Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug 14 days or 5 or more half-lives prior to registration on the study.
• Chronic concomitant treatment with strong CYP3A4 inducers is not allowed. Patients must discontinue the drug 14 days prior to the start of study treatment.

ADDITIONAL REGISTRATION ELIGIBILITY CRITERIA FOR PAXALISIB ARM

• Urine protein to creatinine (UPC) ratio < 1 or urine protein =< 1.
• Recent acute myocardial infarction in the last 6 months or current angina pectoris are excluded. Patients with symptomatic bradycardia should have an electrocardiogram at baseline. If QT interval > 470 msec, the patient is excluded.
• Patients with uncontrolled type I or II diabetes mellitus should be excluded. Uncontrolled diabetes is defined as glycosylated hemoglobin (HbA1c) > 9% in addition to fasting glucose > 140 mg/dL on at least 2 occasions within 14 days prior to registration.

ADDITIONAL REGISTRATION ELIGIBILITY CRITERION FOR ENTRECTINIB ARM

• Concurrent use of H2 receptor antagonists, receptor antagonists, proton pump inhibitors (PPIs), and/or antacids are prohibited.

ADDITIONAL REGISTRATION ELIGIBILITY CRITERION FOR ABEMACICLIB ARM

• Hemoglobin >= g/dL. Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
• Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to registration. A washout period of at least 21 days is required between last chemotherapy dose and registration (provided the patient did not receive radiotherapy).
• Patients who received adjuvant radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy and registration.
• Breast cancer patients who have received ribociclib or palbociclib are eligible as long as there is documentation of CDK4/6 pathway alteration on a biopsy or resection at the point of progression post-ribociclib or palbociclib.
• For females of childbearing potential: A female of childbearing potential, must have a negative serum pregnancy test within 7 days prior to registration and agree to use a highly effective contraception method during the treatment period and for 3 weeks following the last dose of abemaciclib. Contraceptive methods may include an intrauterine device [IUD] or barrier method. If condoms are used as a barrier method, a spermicidal agent should be added as a double barrier protection. Cases of pregnancy that occur during maternal exposures to abemaciclib should be reported. If a patient or spouse/partner is determined to be pregnant following abemaciclib initiation, she must discontinue treatment immediately. Data on fetal outcome and breast-feeding are to be collected for regulatory reporting and drug safety evaluation.
• Patients with active bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive] are excluded. Screening is not required for enrollment.
• Patients with personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest, are excluded.

ADDITIONAL REGISTRATION ELIGIBILITY CRITERION FOR ADAGRASIB (MRTX849) ARM

• Hemoglobin ≥9.0 g/dL. Note: Transfusions will be allowed to achieve this provided the patient has not received more than 2 units of red blood cells in the prior 4 weeks.
• Any of the following cardiovascular abnormalities within 6 months of study entry are excluded: symptomatic or uncontrolled atrial fibrillation, unstable angina pectoris or myocardial infarction, CHF ≥ NYHA Class 3, stroke or transient ischemic attack.
• Ongoing need for medication known to cause prolonged QTc interval or that are substrates of CYP3A4 with narrow therapeutic index that cannot be switched to alternative treatment prior to study entry is excluded.
• Prolonged QTc interval >480 milliseconds or family history or medical history of Long QT syndrome is excluded.•

• Known human immunodeficiency virus (HIV) infection or acute or chronic hepatitis B or C infection is excluded. Screening is not required for enrollment. Note that the following are permitted:

  • Patients treated for hepatitis C (HCV) with no detectable viral load;
  • Patients treated for HIV with no detectable viral load for at least 1 month prior to randomization while on a stable regimen of agents that are not strong inhibitors of CYP3A4; and
  • Patients with hepatitis B (HBV) receiving prophylaxis against reactivation of hepatitis B (either [HBsAg-positive with normal ALT and HBV DNA <2,000 IU/mL or <10,000 copies/mL] or [HBsAg-negative and anti-HBc positive]).
• History of intestinal disease or major gastric surgery likely to alter absorption of study treatment or inability to swallow oral medications is excluded.
• Recovery from the adverse effects of prior therapy to baseline or Grade 1 (any grade alopecia and Grade ≤2 peripheral neuropathy are eligible).
• For females of childbearing potential. It is not known whether MRTX849 presents a risk to the embryo or the fetus; however, based on the mechanism of action (KRAS G12C inhibition), effects on the reproductive system are not unexpected. MRTX849 is contraindicated in women who are pregnant or lactating. Women of childbearing potential and men receiving MRTX849 who are sexually active must employ an effective method of contraception throughout their period of treatment and for 6 months after their last treatment with MRTX849.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (CDK gene mutation); Patients receive abemaciclib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Abemaciclib; Given PO
Experimental: Arm II (PI3K gene mutation); Patients receive PI3K inhibitor paxalisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: PI3K Inhibitor paxalisib; Given PO
Experimental: Arm III (NTRK/ROS1 gene mutation); Patients receive entrectinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Entrectinib; Given PO
Experimental: Arm IV (KRAS G12C mutation); Patients receive adagrasib (MRTX849) PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Drug: Adagrasib; Given PO; Other Names: MRTX849

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate in the brain	Assessed per Response Assessment in Neuro-Oncology (RANO) criteria for brain metastases. The response rate is defined as the number of patients who have achieved complete response (CR) or partial response (PR) per RANO for brain metastases criteria during treatment with CDK, PI3K, NTRK/ROS, or KRAS G12C inhibitors divided by total number of evaluable patients. The response rate and associated exact confidence interval will be estimated within each cohort defined by the targeted agent and histology.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic response for extracranial disease	Assessed with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Will be estimated using the systemic response rate (SRR) - where SRR is defined as the number of evaluable patients achieving a response (PR or CR per RECIST 1.1) during treatment with study therapy divided by the total number of evaluable patients. Point estimates will be generated for systemic response rates within each cohort with corresponding 95% binomial confidence intervals.	Up to 5 years
Clinical benefit rate for central nervous system (CNS)	Evaluated by Response Assessment in Neuro-Oncology (RANO) criteria. Will be estimated as the number of evaluable patients achieving stable disease (SD), partial response (PR), or complete response (CR) as their best objective response during treatment with protocol therapy divided by the total number of evaluable patients. Point estimates will be generated for clinical benefit rates within each cohort with corresponding 95% binomial confidence intervals.	Up to 5 years
Clinical benefit rate for extracranial disease	Assessed by Response Evaluation Criteria in Solid Tumors (RECIST). Will be estimated as the number of evaluable patients achieving stable disease (SD), partial response (PR), or complete response (CR) as their best objective response (per RECIST for extracranial disease) during treatment with protocol therapy divided by the total number of evaluable patients. Point estimates will be generated for clinical benefit rates within each cohort with corresponding 95% binomial confidence intervals.	Up to 5 years
Duration of response for brain metastases	Duration of response for brain metastases is defined for all evaluable patients who have achieved a confirmed response as the time from the date at which the patient's objective status for brain metastases is first noted to be a CR or PR (per Response Assessment in Neuro-Oncology [RANO] for brain metastases) to the date of the earliest progressive CNS disease is documented or death. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.	From the time measurement criteria are met for CR or PR for brain metastases until the first date that progressive CNS disease or death is documented, assessed up to 5 years
Duration of response for extracranial disease	Duration of response for extracranial disease is defined for all evaluable patients who have achieved a confirmed response as the time from the date at which the patient's objective status for extranial disease is first noted to be a CR or PR (per RECIST1.1) to the date of the earliest progression (PD) for extracranial disease is documented or death. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.	From the time measurement criteria are met for CR or PR for extracranial disease until the first date that progressive disease for extracranial disease or death is documented, assessed up to 5 years
Progression-free survival (PFS) - intracranial	Intracranial PFS is defined as the time from the first day of study treatment to the earliest date of intracranial disease progression (per RANO for brain metastases) or death from any cause, whichever comes first. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.	From first day of study treatment to the earliest date documentation of intracranial disease progression or death from any cause, assessed up to 5 years
Progression-free survival (PFS) - extracranial	Extracranial PFS is defined as the time from the first day of study treatment to the earliest date of extracranial disease progression (per RECIST1.1) or death from any cause, whichever comes first. The median and 95% confidence intervals will be estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.	From the first day of study treatment to the earliest date of documentation of extracranial disease progression or death from any cause, assessed up to 5 years
Site of first progression	The site of first progression will be estimated descriptively within each cohort within 12 and 24 months after starting protocol treatment. The first progression is defined as the first documented central nervous system (CNS) progression per Response Assessment in Neuro-Oncology (RANO) or extracranial progression per Response Evaluation Criteria in Solid Tumors (RECIST), whichever occurs first. The percentage of extracranial progression at first progression within 12 and 24 months after starting protocol treatment will be estimated as number of patients who experience the first progression which is extracranial progression divided by number of patients who are still at risk up to 12 and 24 months, respectively.	Up to 24 months
Overall survival	Overall survival is defined as the time from the first day of study treatment to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. No formal comparison will be made among the cohorts.	From the first day of study treatment to death due to any cause, assessed up to 5 years
Incidence of adverse events	Assessed per National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, toxicity is defined as adverse events that are classified as possibly, probably, or definitely related to study treatment. Toxicities will be evaluated via the ordinal CTCAE standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by patient and treatment cohort will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of the analysis. No formal comparison will be made among the cohorts.	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI); Eli Lilly and Company; Genentech, Inc.; Kazia Therapeutics Limited; Mirati Therapeutics Inc.
• Investigators: Study Chair: Priscilla Brastianos, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• Sammons S, Van Swearingen AED, Anders CK. Receptor discordance in breast cancer brain metastases: when knowledge is power. Neuro Oncol. 2020 Aug 17;22(8):1060-1061. doi: 10.1093/neuonc/noaa131. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: June 14, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Nervous System Neoplasms; Central Nervous System Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Brain Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; abemaciclib; adagrasib; entrectinib
• Other Study ID Numbers: A071701; U10CA180821 (U.S. NIH Grant/Contract); NCI-2019-00744 (Registry Identifier: NCI Clinical Trial Reporting Program)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No