Study of Chemotherapy Plus Ipatasertib for People With Solid Tumors With PTEN/AKT Mutations, A ComboMATCH Treatment Trial

Phase 2 Study of Paclitaxel (NSC #673089) + Ipatasertib (NSC #781451) in Taxane-Refractory Participants With PTEN/AKT-Altered Advanced Non-Breast Solid Tumors: A ComboMATCH Treatment Trial

This phase II ComboMATCH treatment trial tests the usual treatment of chemotherapy (paclitaxel) plus ipatasertib in patients with solid tumor cancers that that cannot be removed by surgery (unresectable), has spread to nearby tissue or lymph nodes (locally advanced) or from where it first started (primary site) to other places in the body (metastatic), and has PTEN and AKT genetic changes. Chemotherapy drugs, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Targeted therapy, such as Ipatasertib, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of ipatasertib to paclitaxel in solid tumors with PTEN and AKT genetic changes could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression). Researchers hope to learn if paclitaxel plus ipatasertib will shrink this type of cancer or stop its growth.

Study Overview

• Status: Suspended
• Conditions: Locally Advanced Malignant Solid Neoplasm; Unresectable Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Drug: Ipatasertib; Procedure: Computed Tomography; Procedure: Biospecimen Collection; Procedure: Biopsy Procedure

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the overall response rate (ORR) (confirmed and unconfirmed, complete, and partial) with the combination of paclitaxel plus ipatasertib in participants with advanced PTEN/AKT-altered non-breast solid tumors who have previously progressed on taxane-based therapy

SECONDARY OBJECTIVES:

I. To assess the progression-free survival (PFS) in the study population. II. To assess the duration of response (DoR) in participants who respond to treatment.

III. To assess the overall survival (OS) in the study population. IV. To evaluate the frequency and severity of toxicities related to the combination therapy.

V. Collect tissue and provide it to the ComboMATCH Registration protocol to assess concordance between the diagnostic tumor mutation profile generated by the designated laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor deoxyribonucleic acid (ctDNA) mutation profile from plasma, as described in ComboMATCH Registration protocol. For this treatment substudy, the outcome objective will be to report the proportion of cases providing sufficient tissue for that integrated scientific activity in the ComboMATCH Registration protocol.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To conduct whole exome sequencing (WES) and ribonucleic acid (RNA) sequencing (RNAseq) analysis of tumors at baseline (mandatory), as well as PTEN expression analysis of tumors at baseline (2nd priority after nucleic acid for WES and RNAseq).

II. To explore changes in plasma PTEN/AKT mutation allelic burden and other molecular findings at baseline (mandatory) and upon progression (optional) using ctDNA and correlate changes with response/resistance to therapy.

III. To perform comprehensive protein expression and function analysis on fresh frozen specimens (optional) collected at baseline and at progression to assess determinants of response and resistance to therapy.

OUTLINE:

Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15 and ipatasertib orally (PO) on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a computed tomography (CT) or magnetic resonance imaging (MRI) and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up.

After completion of study treatment, patients are followed until death or 3 years after registration, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Bayamón, Puerto Rico, 00961
    • Puerto Rico Hematology Oncology Group
  • San Juan, Puerto Rico, 00927
    • Centro Comprensivo de Cancer de UPR
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
    • Mobile, Alabama, United States, 36688
      • University of South Alabama Mitchell Cancer Institute
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care
  • Arizona
    • Kingman, Arizona, United States, 86401
      • Kingman Regional Medical Center
  • California
    • Arroyo Grande, California, United States, 93420
      • PCR Oncology
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic and Research Institute - West Los Angeles Office
    • Orange, California, United States, 92868
      • Saint Joseph Hospital - Orange
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Santa Monica, California, United States, 90404
      • Saint John's Cancer Institute
  • Florida
    • Aventura, Florida, United States, 33180
      • UM Sylvester Comprehensive Cancer Center at Aventura
    • 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
    • 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
    • Miami, Florida, United States, 33176
      • UM Sylvester Comprehensive Cancer Center at Kendall
    • Plantation, Florida, United States, 33324
      • UM Sylvester Comprehensive Cancer Center at Plantation
  • 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
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Cancer Institute - Fruitland
    • 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
    • Barrington, Illinois, United States, 60010
      • Advocate Good Shepherd Hospital
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Chicago, Illinois, United States, 60657
      • Advocate Illinois Masonic Medical Center
    • Crystal Lake, Illinois, United States, 60014
      • AMG Crystal Lake - Oncology
    • Danville, Illinois, United States, 61832
      • Carle at The Riverfront
    • 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
    • Hazel Crest, Illinois, United States, 60429
      • Advocate South Suburban Hospital
    • Libertyville, Illinois, United States, 60048
      • Condell Memorial Hospital
    • Libertyville, Illinois, United States, 60048
      • AMG Libertyville - Oncology
    • Mattoon, Illinois, United States, 61938
      • Carle Physician Group-Mattoon/Charleston
    • New Lenox, Illinois, United States, 60451
      • UC Comprehensive Cancer Center at Silver Cross
    • Oak Lawn, Illinois, United States, 60453-2699
      • Advocate Christ Medical Center
    • Orland Park, Illinois, United States, 60462
      • University of Chicago Medicine-Orland Park
    • Park Ridge, Illinois, United States, 60068
      • Advocate Lutheran General Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Iowa
    • Ankeny, Iowa, United States, 50023
      • UI Health Care Mission Cancer and Blood - Ankeny Clinic
    • Des Moines, Iowa, United States, 50314
      • Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50309
      • UI Health Care Mission Cancer and Blood - Des Moines Clinic
    • Waukee, Iowa, United States, 50263
      • UI Health Care Mission Cancer and Blood - Waukee Clinic
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
  • Maine
    • Augusta, Maine, United States, 04330
      • Harold Alfond Center for Cancer Care
    • Brewer, Maine, United States, 04412
      • Lafayette Family Cancer Center-EMMC
    • Scarborough, Maine, United States, 04074
      • MaineHealth Maine Medical Center- Scarborough
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center
    • Cumberland, Maryland, United States, 21502
      • UPMC Western Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
    • Brighton, Michigan, United States, 48114
      • Trinity Health IHA Medical Group Hematology Oncology - Brighton
    • Brighton, Michigan, United States, 48114
      • Trinity Health Medical Center - Brighton
    • Canton, Michigan, United States, 48188
      • Trinity Health IHA Medical Group Hematology Oncology - Canton
    • Canton, Michigan, United States, 48188
      • Trinity Health Medical Center - Canton
    • Chelsea, Michigan, United States, 48118
      • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
    • Chelsea, Michigan, United States, 48118
      • Chelsea Hospital
    • Dearborn, Michigan, United States, 48124
      • Corewell Health Dearborn Hospital
    • Farmington Hills, Michigan, United States, 48336
      • Corewell Health Farmington Hills 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
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Macomb, Michigan, United States, 48044
      • Henry Ford Saint John Hospital - Macomb Medical
    • Pontiac, Michigan, United States, 48341
      • Trinity Health Saint Joseph Mercy Oakland Hospital
    • Royal Oak, Michigan, United States, 48073
      • Corewell Health William Beaumont University Hospital
    • Saginaw, Michigan, United States, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • Saginaw, Michigan, United States, 48601
      • MyMichigan Medical Center Saginaw
    • Tawas City, Michigan, United States, 48764
      • MyMichigan Medical Center Tawas
    • Troy, Michigan, United States, 48085
      • Corewell Health Beaumont Troy Hospital
    • West Branch, Michigan, United States, 48661
      • Saint Mary's Oncology/Hematology Associates of West Branch
    • Ypsilanti, Michigan, United States, 48197
      • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Ypsilanti, Michigan, United States, 48106
      • Huron Gastroenterology PC
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • Sanford Joe Lueken Cancer Center
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Deer River, Minnesota, United States, 56636
      • Essentia Health - Deer River Clinic
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Hibbing, Minnesota, United States, 55746
      • Essentia Health Hibbing Clinic
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • 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
    • Sandstone, Minnesota, United States, 55072
      • Essentia Health Sandstone
    • Virginia, Minnesota, United States, 55792
      • Essentia Health Virginia Clinic
  • 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
      • Benefis Sletten Cancer Institute
    • Kalispell, Montana, United States, 59901
      • Logan Health Medical Center
    • Missoula, Montana, United States, 59804
      • Community Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • OptumCare Cancer Care at Charleston
    • Las Vegas, Nevada, United States, 89183
      • OptumCare Cancer Care at Fort Apache
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Broadway Medical Center
  • Ohio
    • Avon, Ohio, United States, 44011
      • UH Seidman Cancer Center at UH Avon Health Center
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Belpre, Ohio, United States, 45714
      • Strecker Cancer Center-Belpre
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • Columbus, Ohio, United States, 43214
      • Columbus Oncology and Hematology Associates Inc
    • Columbus, Ohio, United States, 43228
      • Doctors Hospital
    • Columbus, Ohio, United States, 43213
      • Mount Carmel East Hospital
    • Columbus, Ohio, United States, 43215
      • Grant Medical Center
    • Dayton, Ohio, United States, 45415
      • Dayton Physician LLC - Englewood
    • 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
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Lancaster, Ohio, United States, 43130
      • Fairfield Medical Center
    • Mansfield, Ohio, United States, 44903
      • OhioHealth Mansfield Hospital
    • Marion, Ohio, United States, 43302
      • OhioHealth Marion General Hospital
    • Marysville, Ohio, United States, 43040
      • Memorial Hospital
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
    • Mount Vernon, Ohio, United States, 43050
      • Knox Community Hospital
    • Newark, Ohio, United States, 43055
      • Licking Memorial Hospital
    • Perrysburg, Ohio, United States, 43551
      • Mercy Health - Perrysburg Hospital
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Springfield, Ohio, United States, 45504
      • Springfield Regional Cancer Center
    • Springfield, Ohio, United States, 45504
      • Springfield Regional Medical Center
    • Toledo, Ohio, United States, 43623
      • Mercy Health - Saint Anne Hospital
    • Westerville, Ohio, United States, 43081
      • Saint Ann's Hospital
    • Westerville, Ohio, United States, 43082
      • OhioHealth Westerville Medical Campus/Westerville Cancer Center
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • 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
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Altoona, Pennsylvania, United States, 16601
      • UPMC Altoona
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Pocono Medical Center
    • Erie, Pennsylvania, United States, 16505
      • UPMC Hillman Cancer Center Erie
    • Greensburg, Pennsylvania, United States, 15601
      • UPMC Cancer Centers - Arnold Palmer Pavilion
    • Hazleton, Pennsylvania, United States, 18201
      • Lehigh Valley Hospital-Hazleton
    • Mechanicsburg, Pennsylvania, United States, 17050
      • UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
    • Media, Pennsylvania, United States, 19063
      • Riddle Memorial Hospital
    • Monroeville, Pennsylvania, United States, 15146
      • UPMC Hillman Cancer Center - Monroeville
    • Paoli, Pennsylvania, United States, 19301
      • Paoli Memorial Hospital
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC-Magee Womens Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
    • Pittsburgh, Pennsylvania, United States, 15237
      • UPMC-Passavant Hospital
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Richmond, Virginia, United States, 23235
      • VCU Massey Cancer Center at Stony Point
    • Richmond, Virginia, United States, 23229
      • Virginia Cancer Institute
    • Richmond, Virginia, United States, 23298
      • VCU Massey Comprehensive Cancer Center
    • Roanoke, Virginia, United States, 24033
      • Carilion Roanoke Memorial Hospital
    • South Hill, Virginia, United States, 23970
      • VCU Community Memorial Health Center
  • Washington
    • Edmonds, Washington, United States, 98026
      • Swedish Cancer Institute-Edmonds
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Renton, Washington, United States, 98055
      • Valley Medical Center
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
  • Wisconsin
    • Ashland, Wisconsin, United States, 54806
      • Duluth Clinic Ashland
    • 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
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Medical Center
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center - University Hospital
    • Madison, Wisconsin, United States, 53718
      • University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
    • Marinette, Wisconsin, United States, 54143
      • Aurora Bay Area Medical Group-Marinette
    • 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
    • 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
    • Wauwatosa, Wisconsin, United States, 53226
      • Aurora Cancer Care-Milwaukee West
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-S3 based on the presence of an actionable mutation as defined in EAY191
• GENERAL COMBOMATCH EAY191 REGISTRATION INCLUSION CRITERIA:
• Participants must be enrolled on the ComboMATCH Master Registration Trial EAY191
• Participants must have an activating AKT mutation (a known mutation in AKT1, AKT2, or AKT3, a single nucleotide variant, insertion, or deletion), PTEN mutation (a known mutation in PTEN, a single nucleotide variant, insertion, or deletion), or genomic deletion loss of PTEN as determined by the ComboMATCH screening assessment
• GENERAL COMBOMATCH EAY191 REGISTRATION EXCLUSION CRITERIA:
• Participants must not have an activating KRAS, NRAS, HRAS, or BRAF mutation (a single nucleotide variant, insertion, or deletion) as determined by the ComboMATCH screening assessment
• Participants must have disease that can be safely biopsied and agree to a pre-treatment biopsy or have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191)
• Participants must have a histologically confirmed non-breast solid malignancy
• Participants must have locally advanced, unresectable, or metastatic disease in the opinion of the treating investigator
• Participants must have measurable disease documented by CT or MRI. Measurable disease must be assessed within 28 days prior to registration. Non-measurable disease must be assessed within 42 days prior to registration. The CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration
• Participants with known brain metastases must have a CT/MRI scan to evaluate for central nervous system (CNS) disease and show no evidence of progression within 42 days prior to registration
• Participants must have completed any CNS-directed therapy and/or local therapy for spinal cord compression at least 28 days prior to registration
• Participants must not have spinal cord compression or brain metastases unless: (1) metastases have been locally treated and have remained clinically controlled and asymptomatic for at least 14 days prior to registration, AND (2) participant has no residual neurological dysfunction and has been off corticosteroids for at least 24 hours prior to registration
• Participants must not have leptomeningeal disease
• Participants must have progressed on or within 6 months of taxane-based therapy in the neoadjuvant/adjuvant or metastatic setting prior to registration
• Participants must not have received any prior AKT inhibitor (e.g., capivasertib or ipatasertib); prior PI3K/mTOR inhibitor is acceptable
• Participants must not have received cancer-directed therapy prior for at least 14 days prior to initiation of treatment on study
• Participants must not be planning to receive any concurrent chemotherapy, immunotherapy, biologic, radiation, or hormonal therapy for cancer treatment while receiving treatment on this study
• Participants must be >= 18 years of age
• Participants must be able to swallow oral medications whole
• Participants must have a pre-study history and physical exam done within 28 days prior to registration
• Participants must have a Zubrod performance status of 0-2 within 28 days prior to registration
• Participants must have adverse events resolved =< grade 1 related to any prior therapy, except alopecia within 14 days prior to registration
• Participants with neuropathy must have resolved to < grade 2 within 14 days prior to registration
• Leukocytes >= 3 x 10^3/uL (within 28 days prior to registration)
• Absolute neutrophil count >= 1.5 x 10^3/uL (within 28 days prior to registration)
• Platelets >= 100 x 10^3/uL (within 28 days prior to registration)
• Total bilirubin =< institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin =< 5 x institutional ULN (within 28 days prior to registration)
• Aspartate aminotransferase (AST) & alanine aminotransferase (ALT) =< 3 x institutional ULN (within 28 days prior to registration)
• Participants must have adequate cardiac function, class IIB (2B) or better. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification
• Participants must have a measured OR calculated creatinine clearance >= 50 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn within 28 days prior to registration
• Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have an undetectable viral load test on the most recent test results obtained within 6 months prior to registration
• Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to registration
• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within 28 days prior to registration
• Participants must have an electrocardiography (ECG) performed (if clinically indicated with a corrected QTc interval of =< 470 msec) within 28 days prior to registration
• Participants must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to ipatasertib and/or paclitaxel
• Participants must not have an active small/large bowel inflammation such as ulcerative colitis or Crohn's disease

• Participants must not have grade 2 or higher uncontrolled intercurrent illness

  • NOTE: To receive an agent, participant must not have any uncontrolled intercurrent illness requiring antibiotic/antiviral/antifungal therapy or interventional procedures. Participants with infections unlikely to be resolved within 2 weeks following registration should not be considered for the trial
• Participants must not have a known grade 2 or higher uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia

• Participants must not have any of the following:

  • Cirrhosis at a level of Child-Pugh B (or worse),
  • Cirrhosis (any degree) and a history of hepatic encephalopathy, or
  • Clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis

• Participants must not be receiving any medications or substances that are inhibitors or inducers of CYP3A. Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of study drug is prohibited.

  • NOTE: Because the lists of these agents are constantly changing, it is important to regularly consult a frequently updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product. The participant wallet card should be presented to the participant
• Participants must not have baseline fasting glucose (after 8-hour fast) > 160 mg/dL (8.9 mmol/L) within 28 days prior to registration
• Participants with known diabetes mellitus must not require insulin therapy or have a baseline fasting glucose >150 mg/dL (8.3 mmol/L) or high glycosylated hemoglobin (Hb)A1c, (>= 8.0%), suggesting poorly controlled diabetes
• Participants who are on a stable dose of oral diabetes medication >= 2 weeks prior to initiation of study drug treatment are eligible for enrollment
• Participants with a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) must not have a potential to interfere with the safety or efficacy assessment of the investigational regimen
• Participants must not have lung disease requiring active systemic therapy or placing participants at increased risk of toxicity related to study-directed therapy including, but not limited to pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
• Participants must not be pregnant or nursing. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is of "reproductive potential". In addition to routine contraceptive methods, "effective contraception" also includes surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen
• Participants must not have psychiatric illness/social situations that would limit compliance with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (paclitaxel, ipatasertib); Patients receive paclitaxel IV on days 1, 8, and 15 and ipatasertib PO on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Asotax; Bristaxol; Praxel; Taxol Konzentrat; Drug: Ipatasertib; Given PO; Other Names: GDC-0068; RG7440; RG-7440; GDC 0068; GDC0068; RG 7440; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Procedure: Biospecimen Collection; Undergo blood collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Sample Collection; Procedure: Biopsy Procedure; Undergo tumor biopsy; Other Names: Bx; BIOPSY_TYPE; Biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	The proportion of participants who have a partial or complete response (confirmed or unconfirmed) as best response.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Response rates and associated confidence intervals will be calculated. Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median times.	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years
Overall survival	Response rates and associated confidence intervals will be calculated. Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median times.	From date of registration to date of death due to any cause, assessed up to 3 years
Duration of response	Response rates and associated confidence intervals will be calculated. Will be estimated using the method of Kaplan-Meier. The Brookmeyer-Crowley method will be used to calculate confidence intervals for median times.	From date of first documentation of response (complete response, partial response, confirmed or unconfirmed) to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Reva K Basho, SWOG Cancer Research Network

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2023
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: September 22, 2022
• First Submitted That Met QC Criteria: September 22, 2022
• First Posted (Actual): September 26, 2022

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Organic Chemicals; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Health Care Economics and Organizations; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Economics; Paclitaxel; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; ipatasertib; Taxes
• Other Study ID Numbers: NCI-2022-07304 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180888 (U.S. NIH Grant/Contract); EAY191-S3 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

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