Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)

August 28, 2024 updated by: National Cancer Institute (NCI)

A Randomized Trial of Neratinib, A Pan-ERBB Inhibitor, Alone or in Combination With Palbociclib, a CDK4/6 Inhibitor, in Patients With HER2+ Gynecologic Cancers and Other Solid Tumors: A ComboMATCH Treatment Trial

This phase II ComboMATCH treatment trial compares the effect of neratinib to the combination of neratinib and palbociclib in treating patients with HER2 positive solid tumors. Neratinib and palbociclib are in a class of medications called kinase inhibitors. They work by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of tumor cells. Giving neratinib and palbociclib in combination may shrink or stabilize cancers that over-express a specific biomarker called HER2.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. To investigate the efficacy of neratinib plus palbociclib (PD-0332991) compared to neratinib maleate (neratinib) alone in patients with HER2+ gynecologic cancers and HER2+ solid tumors by evaluating progression-free survival (PFS).

SECONDARY OBJECTIVES:

I. To investigate outcome in terms of objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. To investigate clinical benefit rate (ORR + stable disease at 16 weeks). III. To evaluate overall (OS) survival. IV. To evaluate the ORR of patients who crossed over from neratinib monotherapy to neratinib-palbociclib combination.

V. To investigate adverse events especially grade 3 and 4 toxicities by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

VI. 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-derived deoxyribonucleic acid (ctDNA) mutation profile from plasma, as described in ComboMATCH Registration Protocol.

EXPLORATORY TRANSLATIONAL OBJECTIVES:

I. To investigate the role of ctDNA-HER2 status at baseline and during follow up to assess if it predicts response to therapy and disease progression and if it does correlate with tumor tissue based HER2 status.

II. To investigate if activation of the pathways of interest (PI3K/mTOR and RB1, CCND1-CDK4/6 CDK and RAS/RAF/MAPK) in tumor tissue as well as blood/ctDNA correlate with response or resistance to therapy.

III. To correlate extent of HER2 amplification with response to treatment and with HER2 expression by immunohistochemistry or fluorescence in situ hybridization (FISH).

IV. To correlate the extent of HER2 amplification with HER2 expression by RNA and protein immunohistochemistry (IHC) analyses and FISH.

V. To correlate expression of Rb1, CCND1, CCNE1, CDK4/6 protein expression with response to treatment.

VI. Assess alteration in RB1-CDK pathway in neratinib resistant patients at time of progression on monotherapy compared to combination neratinib-palbociclib.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive neratinib maleate orally (PO) once daily (QD) on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) during screening and on study, and computed tomography (CT) or magnetic resonance imaging (MRI) and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.

ARM II: Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama at Birmingham Cancer Center
        • Contact:
        • Principal Investigator:
          • Rebecca C. Arend
    • Idaho
      • Boise, Idaho, United States, 83706
        • Recruiting
        • Saint Alphonsus Cancer Care Center-Boise
        • Contact:
        • Principal Investigator:
          • John M. Schallenkamp
      • Caldwell, Idaho, United States, 83605
        • Recruiting
        • Saint Alphonsus Cancer Care Center-Caldwell
        • Contact:
        • Principal Investigator:
          • John M. Schallenkamp
      • Coeur d'Alene, Idaho, United States, 83814
        • Recruiting
        • Kootenai Health - Coeur d'Alene
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Nampa, Idaho, United States, 83687
        • Recruiting
        • Saint Alphonsus Cancer Care Center-Nampa
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Post Falls, Idaho, United States, 83854
        • Recruiting
        • Kootenai Clinic Cancer Services - Post Falls
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Sandpoint, Idaho, United States, 83864
        • Recruiting
        • Kootenai Clinic Cancer Services - Sandpoint
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Recruiting
        • John H Stroger Jr Hospital of Cook County
        • Contact:
          • Site Public Contact
          • Phone Number: 312-864-5204
        • Principal Investigator:
          • Thomas E. Lad
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Cancer Care Specialists of Illinois - Decatur
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Decatur, Illinois, United States, 62526
        • Recruiting
        • Decatur Memorial Hospital
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Effingham, Illinois, United States, 62401
        • Recruiting
        • Crossroads Cancer Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Southern Illinois University School of Medicine
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 217-545-7929
      • Springfield, Illinois, United States, 62702
        • Recruiting
        • Springfield Clinic
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 800-444-7541
      • Springfield, Illinois, United States, 62781
        • Recruiting
        • Memorial Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
    • Iowa
      • Ankeny, Iowa, United States, 50023
        • Recruiting
        • Mission Cancer and Blood - Ankeny
        • Principal Investigator:
          • Richard L. Deming
        • Contact:
          • Site Public Contact
          • Phone Number: 515-282-2921
      • Des Moines, Iowa, United States, 50309
        • Recruiting
        • Mission Cancer and Blood - Des Moines
        • Contact:
          • Site Public Contact
          • Phone Number: 515-241-3305
        • Principal Investigator:
          • Seema Harichand-Herdt
    • Maine
      • Brewer, Maine, United States, 04412
        • Recruiting
        • Lafayette Family Cancer Center-EMMC
        • Principal Investigator:
          • Sarah J. Sinclair
        • Contact:
          • Site Public Contact
          • Phone Number: 800-987-3005
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-411-1222
        • Principal Investigator:
          • Sarah Shin
      • Cumberland, Maryland, United States, 21502
        • Recruiting
        • UPMC Western Maryland
        • Contact:
          • Site Public Contact
          • Phone Number: 240-964-1400
        • Principal Investigator:
          • Haider S. Mahdi
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • Recruiting
        • Trinity Health Saint Joseph Mercy Hospital Ann Arbor
        • Contact:
        • Principal Investigator:
          • Tareq Al Baghdadi
      • Brighton, Michigan, United States, 48114
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Brighton
        • Contact:
        • Principal Investigator:
          • Tareq Al Baghdadi
      • Canton, Michigan, United States, 48188
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Canton
        • Contact:
        • Principal Investigator:
          • Tareq Al Baghdadi
      • Chelsea, Michigan, United States, 48118
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
        • Contact:
        • Principal Investigator:
          • Tareq Al Baghdadi
      • Dearborn, Michigan, United States, 48124
        • Recruiting
        • Corewell Health Dearborn Hospital
        • Principal Investigator:
          • Dana Zakalik
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
      • Farmington Hills, Michigan, United States, 48336
        • Recruiting
        • Corewell Health Farmington Hills Hospital
        • Principal Investigator:
          • Dana Zakalik
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Cancer and Blood Disease Treatment Center
        • Contact:
        • Principal Investigator:
          • Tareq Al Baghdadi
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesee Hematology Oncology PC
        • Contact:
        • Principal Investigator:
          • Tareq Al Baghdadi
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Genesys Hurley Cancer Institute
        • Contact:
        • Principal Investigator:
          • Tareq Al Baghdadi
      • Flint, Michigan, United States, 48503
        • Recruiting
        • Hurley Medical Center
        • Contact:
        • Principal Investigator:
          • Tareq Al Baghdadi
      • Lansing, Michigan, United States, 48912
        • Recruiting
        • University of Michigan Health - Sparrow Lansing
        • Principal Investigator:
          • Tareq Al Baghdadi
        • Contact:
      • Livonia, Michigan, United States, 48154
        • Recruiting
        • Trinity Health Saint Mary Mercy Livonia Hospital
        • Contact:
        • Principal Investigator:
          • Tareq Al Baghdadi
      • Royal Oak, Michigan, United States, 48073
        • Recruiting
        • Corewell Health William Beaumont University Hospital
        • Principal Investigator:
          • Dana Zakalik
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
      • Troy, Michigan, United States, 48085
        • Recruiting
        • Corewell Health Beaumont Troy Hospital
        • Principal Investigator:
          • Dana Zakalik
        • Contact:
          • Site Public Contact
          • Phone Number: 248-551-7695
      • Ypsilanti, Michigan, United States, 48197
        • Recruiting
        • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
        • Contact:
        • Principal Investigator:
          • Tareq Al Baghdadi
    • Minnesota
      • Deer River, Minnesota, United States, 56636
        • Recruiting
        • Essentia Health - Deer River Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Duluth, Minnesota, United States, 55805
        • Recruiting
        • Essentia Health Cancer Center
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Hibbing, Minnesota, United States, 55746
        • Recruiting
        • Essentia Health Hibbing Clinic
        • Principal Investigator:
          • Bret E. Friday
        • Contact:
          • Site Public Contact
          • Phone Number: 218-786-3308
      • Maplewood, Minnesota, United States, 55109
        • Recruiting
        • Saint John's Hospital - Healtheast
        • Contact:
        • Principal Investigator:
          • Yan Ji
      • Sandstone, Minnesota, United States, 55072
        • Recruiting
        • Essentia Health Sandstone
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Virginia, Minnesota, United States, 55792
        • Recruiting
        • Essentia Health Virginia Clinic
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
    • Missouri
      • Cape Girardeau, Missouri, United States, 63703
        • Recruiting
        • Saint Francis Medical Center
        • Principal Investigator:
          • Bryan A. Faller
        • Contact:
          • Site Public Contact
          • Phone Number: 573-334-2230
          • Email: sfmc@sfmc.net
    • Montana
      • Anaconda, Montana, United States, 59711
        • Recruiting
        • Community Hospital of Anaconda
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Billings, Montana, United States, 59101
        • Recruiting
        • Billings Clinic Cancer Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Bozeman, Montana, United States, 59715
        • Recruiting
        • Bozeman Health Deaconess Hospital
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Great Falls, Montana, United States, 59405
        • Recruiting
        • Benefis Sletten Cancer Institute
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Kalispell, Montana, United States, 59901
        • Recruiting
        • Kalispell Regional Medical Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
      • Missoula, Montana, United States, 59804
        • Recruiting
        • Community Medical Center
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
    • Nevada
      • Henderson, Nevada, United States, 89052
        • Recruiting
        • OptumCare Cancer Care at Seven Hills
        • Contact:
        • Principal Investigator:
          • John A. Ellerton
      • Las Vegas, Nevada, United States, 89102
        • Recruiting
        • OptumCare Cancer Care at Charleston
        • Contact:
        • Principal Investigator:
          • John A. Ellerton
      • Las Vegas, Nevada, United States, 89148
        • Recruiting
        • OptumCare Cancer Care at Fort Apache
        • Contact:
        • Principal Investigator:
          • John A. Ellerton
    • New Jersey
      • Jersey City, New Jersey, United States, 07302
        • Recruiting
        • Jersey City Medical Center
        • Contact:
        • Principal Investigator:
          • Eugenia Girda
      • Lakewood, New Jersey, United States, 08701
        • Recruiting
        • Monmouth Medical Center Southern Campus
        • Contact:
        • Principal Investigator:
          • Eugenia Girda
      • Long Branch, New Jersey, United States, 07740
        • Recruiting
        • Monmouth Medical Center
        • Contact:
        • Principal Investigator:
          • Eugenia Girda
      • New Brunswick, New Jersey, United States, 08903
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
        • Contact:
          • Site Public Contact
          • Phone Number: 732-235-7356
        • Principal Investigator:
          • Eugenia Girda
      • Toms River, New Jersey, United States, 08755
        • Recruiting
        • Community Medical Center
        • Contact:
        • Principal Investigator:
          • Eugenia Girda
    • New York
      • Syracuse, New York, United States, 13210
        • Recruiting
        • State University of New York Upstate Medical University
        • Contact:
          • Site Public Contact
          • Phone Number: 315-464-5476
        • Principal Investigator:
          • Mary J. Cunningham
    • North Carolina
      • Clinton, North Carolina, United States, 28328
        • Recruiting
        • Southeastern Medical Oncology Center-Clinton
        • Contact:
        • Principal Investigator:
          • Samer S. Kasbari
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
        • Principal Investigator:
          • Angeles A. Secord
        • Contact:
          • Site Public Contact
          • Phone Number: 888-275-3853
      • Goldsboro, North Carolina, United States, 27534
        • Recruiting
        • Southeastern Medical Oncology Center-Goldsboro
        • Contact:
        • Principal Investigator:
          • Samer S. Kasbari
      • Jacksonville, North Carolina, United States, 28546
        • Recruiting
        • Southeastern Medical Oncology Center-Jacksonville
        • Principal Investigator:
          • Samer S. Kasbari
        • Contact:
      • Raleigh, North Carolina, United States, 27607
        • Recruiting
        • Duke Women's Cancer Care Raleigh
        • Principal Investigator:
          • Angeles A. Secord
        • Contact:
          • Site Public Contact
          • Phone Number: 919-785-4878
    • Ohio
      • Centerville, Ohio, United States, 45459
        • Recruiting
        • Miami Valley Hospital South
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45409
        • Recruiting
        • Miami Valley Hospital
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45415
        • Recruiting
        • Miami Valley Hospital North
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45409
        • Recruiting
        • Premier Blood and Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 937-276-8320
        • Principal Investigator:
          • Tarek M. Sabagh
      • Dayton, Ohio, United States, 45415
        • Recruiting
        • Dayton Physician LLC - Englewood
        • Contact:
        • Principal Investigator:
          • Howard M. Gross
      • Franklin, Ohio, United States, 45005-1066
        • Recruiting
        • Atrium Medical Center-Middletown Regional Hospital
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
      • Greenville, Ohio, United States, 45331
        • Recruiting
        • Miami Valley Cancer Care and Infusion
        • Principal Investigator:
          • Tarek M. Sabagh
        • Contact:
          • Site Public Contact
          • Phone Number: 937-569-7515
      • Kettering, Ohio, United States, 45429
        • Recruiting
        • Kettering Medical Center
        • Contact:
        • Principal Investigator:
          • Howard M. Gross
      • Troy, Ohio, United States, 45373
        • Recruiting
        • Upper Valley Medical Center
        • Contact:
        • Principal Investigator:
          • Tarek M. Sabagh
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • University of Oklahoma Health Sciences Center
        • Contact:
        • Principal Investigator:
          • Sagila George
    • Oregon
      • Ontario, Oregon, United States, 97914
        • Recruiting
        • Saint Alphonsus Cancer Care Center-Ontario
        • Principal Investigator:
          • John M. Schallenkamp
        • Contact:
    • Pennsylvania
      • Altoona, Pennsylvania, United States, 16601
        • Recruiting
        • UPMC Altoona
        • Contact:
        • Principal Investigator:
          • Haider S. Mahdi
      • Erie, Pennsylvania, United States, 16505
        • Recruiting
        • UPMC Hillman Cancer Center Erie
        • Contact:
        • Principal Investigator:
          • Haider S. Mahdi
      • Greensburg, Pennsylvania, United States, 15601
        • Recruiting
        • UPMC Cancer Centers - Arnold Palmer Pavilion
        • Contact:
          • Site Public Contact
          • Phone Number: 724-838-1900
        • Principal Investigator:
          • Haider S. Mahdi
      • Mechanicsburg, Pennsylvania, United States, 17050
        • Recruiting
        • UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
        • Contact:
        • Principal Investigator:
          • Haider S. Mahdi
      • Monroeville, Pennsylvania, United States, 15146
        • Recruiting
        • UPMC Hillman Cancer Center - Monroeville
        • Contact:
        • Principal Investigator:
          • Haider S. Mahdi
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Hospital
        • Contact:
        • Principal Investigator:
          • Mitchell I. Edelson
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • University of Pittsburgh Cancer Institute (UPCI)
        • Contact:
          • Site Public Contact
          • Phone Number: 412-647-8073
        • Principal Investigator:
          • Haider S. Mahdi
      • Pittsburgh, Pennsylvania, United States, 15237
        • Recruiting
        • UPMC-Passavant Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 412-367-6454
        • Principal Investigator:
          • Haider S. Mahdi
      • Willow Grove, Pennsylvania, United States, 19090
        • Recruiting
        • Asplundh Cancer Pavilion
        • Contact:
        • Principal Investigator:
          • Mitchell I. Edelson
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • M D Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Sarina A. Piha-Paul
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Inova Schar Cancer Institute
        • Principal Investigator:
          • Timothy L. Cannon
        • Contact:
      • Falls Church, Virginia, United States, 22042
        • Recruiting
        • Inova Fairfax Hospital
        • Principal Investigator:
          • Timothy L. Cannon
        • Contact:
    • Wisconsin
      • Ashland, Wisconsin, United States, 54806
        • Recruiting
        • Duluth Clinic Ashland
        • Contact:
        • Principal Investigator:
          • Bret E. Friday
      • Green Bay, Wisconsin, United States, 54301
        • Recruiting
        • Saint Vincent Hospital Cancer Center Green Bay
        • Contact:
        • Principal Investigator:
          • Matthew L. Ryan
      • Green Bay, Wisconsin, United States, 54303
        • Recruiting
        • Saint Vincent Hospital Cancer Center at Saint Mary's
        • Contact:
        • Principal Investigator:
          • Matthew L. Ryan
      • La Crosse, Wisconsin, United States, 54601
        • Recruiting
        • Gundersen Lutheran Medical Center
        • Contact:
        • Principal Investigator:
          • Collin D. Driscoll
      • Oconto Falls, Wisconsin, United States, 54154
        • Recruiting
        • Saint Vincent Hospital Cancer Center at Oconto Falls
        • Contact:
        • Principal Investigator:
          • Matthew L. Ryan
      • Sheboygan, Wisconsin, United States, 53081
        • Recruiting
        • Saint Vincent Hospital Cancer Center at Sheboygan
        • Contact:
        • Principal Investigator:
          • Matthew L. Ryan
      • Stevens Point, Wisconsin, United States, 54482
      • Sturgeon Bay, Wisconsin, United States, 54235-1495
        • Recruiting
        • Saint Vincent Hospital Cancer Center at Sturgeon Bay
        • Contact:
        • Principal Investigator:
          • Matthew L. Ryan
      • Weston, Wisconsin, United States, 54476

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • 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-N5 based on the presence of an actionable mutation as defined in EAY191
  • Patients must have a HER2 amplified solid tumor except breast cancer. Patient's cancer must have HER2 amplification as defined with ≥ 7 copies by next generation sequencing (NGS) testing
  • Patients must have recurrent or persistent disease
  • No known evidence of RB1 loss or deletion including copy number loss or deleterious mutation
  • Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or, if disease cannot be safely biopsied, have archival tissue available from within 12 months prior to the date of registration on the ComboMATCH Registration Trial (EAY191)
  • Patients must have measurable disease based on RECIST 1.1. A second measurable lesion outside of the biopsiable lesion is required
  • Patients with treated brain metastases are eligible if follow up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression for 3 months or more and patient is not on steroids and is asymptomatic
  • No known leptomeningeal disease
  • Patients may have received up to 5 prior lines of systemic therapy
  • Prior therapy with trastuzumab or pertuzumab, either alone or in combination, is allowed
  • One prior line of anti-HER2 therapy is allowed except tyrosine kinase inhibitors (TKI) such as neratinib or tucatinib or antibody drug conjugates (ADC) such as DS8201a or T-DM1
  • No prior therapy with CDK4/6 inhibition
  • No cancer directed therapy within 3 weeks prior to registration. For oral therapy, the washout can be reduced to greater than or equal to 5 half lives of the drug
  • Age ≥ 18
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
  • Not pregnant and not nursing
  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3
  • Platelets ≥ 100,000 cells/mm^3
  • Hemoglobin ≥ 9 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin (Hgb) ≥ 9 g/dl is acceptable)
  • Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
  • Total bilirubin level ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional upper limit of normal (ULN)
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • No active infection requiring parenteral antibiotics
  • No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
  • No current evidence of malabsorption or chronic diarrhea or any other significant gastro-intestinal disease (e.g gastrectomy, ileal bypass, Crohn's disease, gastroparesis), associated with moderate to severe diarrhea (grade 2 or more) or inability to tolerate oral therapy
  • No lung disease causing dyspnea at rest
  • No interstitial lung disease with ongoing signs and symptoms at the time of registration
  • No history of allergic reaction to the study agents, compound of similar chemical or biologic composition of the study agents or any of their excipients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm I (neratinib maleate)
Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
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
Procedure: Biopsy
Undergo tumor biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
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
Procedure: Echocardiography
Undergo ECHO
Other Names:
  • EC
Procedure: Multigated Acquisition Scan
Undergo MUGA
Other Names:
  • Blood Pool Scan
  • Equilibrium Radionuclide Angiography
  • Gated Blood Pool Imaging
  • MUGA
  • Radionuclide Ventriculography
  • RNVG
  • SYMA Scanning
  • Synchronized Multigated Acquisition Scanning
  • MUGA Scan
  • Multi-Gated Acquisition Scan
  • Radionuclide Ventriculogram Scan
  • Gated Heart Pool Scan
Drug: Neratinib Maleate
Given PO
Other Names:
  • Nerlynx
  • 2-Butenamide, N-(4-((3-chloro-4-(2-pyridinylmethoxy)phenyl)amino)-3-cyano-7-ethoxy-6-quinolinyl)-4-(dimethylamino)-, (2E)-, (2Z)-2-butenedioate (1:1)
  • HKI-272 Maleate
  • NERATINIB MALEATE ANHYDROUS
Experimental: Arm II (neratinib maleate, palbociclib)
Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection
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
Procedure: Biopsy
Undergo tumor biopsy
Other Names:
  • Bx
  • BIOPSY_TYPE
Drug: Palbociclib
Given PO
Other Names:
  • Ibrance
  • 6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-8h-pyrido(2,3-d)pyrimidin-7-one
  • PD 0332991
  • PD 332991
  • PD 991
  • PD-0332991
  • PD0332991
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
Procedure: Echocardiography
Undergo ECHO
Other Names:
  • EC
Procedure: Multigated Acquisition Scan
Undergo MUGA
Other Names:
  • Blood Pool Scan
  • Equilibrium Radionuclide Angiography
  • Gated Blood Pool Imaging
  • MUGA
  • Radionuclide Ventriculography
  • RNVG
  • SYMA Scanning
  • Synchronized Multigated Acquisition Scanning
  • MUGA Scan
  • Multi-Gated Acquisition Scan
  • Radionuclide Ventriculogram Scan
  • Gated Heart Pool Scan
Drug: Neratinib Maleate
Given PO
Other Names:
  • Nerlynx
  • 2-Butenamide, N-(4-((3-chloro-4-(2-pyridinylmethoxy)phenyl)amino)-3-cyano-7-ethoxy-6-quinolinyl)-4-(dimethylamino)-, (2E)-, (2Z)-2-butenedioate (1:1)
  • HKI-272 Maleate
  • NERATINIB MALEATE ANHYDROUS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival
Time Frame: From study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 2 years
The stratified log-rank statistic will be used to draw inferences about the relative activity of the two regimens. Characterized by medians and Kaplan-Meier (KM) curves.
From study entry to time of progression or death, whichever occurs first, or date of last contact if neither progression nor death has occurred, assessed up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Up to 2 years
The impact of treatment on the hazard of death can be investigated with time dependent covariates.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Haider S Mahdi, NRG Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 7, 2024

Primary Completion (Estimated)

April 30, 2025

Study Completion (Estimated)

April 30, 2025

Study Registration Dates

First Submitted

November 9, 2023

First Submitted That Met QC Criteria

November 9, 2023

First Posted (Actual)

November 13, 2023

Study Record Updates

Last Update Posted (Actual)

August 29, 2024

Last Update Submitted That Met QC Criteria

August 28, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2023-09270 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • U10CA180868 (U.S. NIH Grant/Contract)
  • EAY191-N5 (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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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