Testing the Use of Neratinib or the Combination of Neratinib and Palbociclib Targeted Treatment for HER2+ Solid Tumors (A ComboMATCH Treatment Trial)
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
3 other identifiers
interventional
70
1 country
184
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started May 2024
Typical duration for phase_2
184 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 9, 2023
CompletedFirst Posted
Study publicly available on registry
November 13, 2023
CompletedStudy Start
First participant enrolled
May 7, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 20, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 20, 2027
April 16, 2026
March 1, 2026
2.8 years
November 9, 2023
April 15, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Progression free survival
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 Outcomes (1)
Overall survival
Up to 2 years
Study Arms (2)
Arm I (neratinib maleate)
ACTIVE COMPARATORPatients 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.
Arm II (neratinib maleate, palbociclib)
EXPERIMENTALPatients 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.
Interventions
Undergo tumor biopsy
Undergo CT scan
Undergo ECHO
Undergo MRI
Undergo MUGA
Given PO
Given PO
Undergo collection of blood samples
Eligibility Criteria
You may qualify if:
- 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.
- If IHC is 0 or 1+, patient (pt) is NOT ELIGIBLE regardless of in situ hybridization (ISH)/FISH or next generation sequencing (NGS) status
- If IHC is 3+, pt IS ELIGIBLE regardless of ISH/FISH or NGS status
- If IHC is 2+, ISH/FISH OR NGS must be positive for the patient to be ELIGIBLE. Otherwise, pt is NOT ELIGIBLE
- If IHC is unknown and…
- ISH/FISH is positive, independent of NGS results, the patient IS ELIGIBLE
- ISH/FISH is negative and NGS positive with ≥ 7 copies, the patient IS ELIGIBLE
- 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
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (184)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, 36688, United States
Alaska Women's Cancer Care
Anchorage, Alaska, 99508, United States
UC San Diego Health System - Encinitas
Encinitas, California, 92024, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
The Angeles Clinic and Research Institute - West Los Angeles Office
Los Angeles, California, 90025, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
UC San Diego Medical Center - Hillcrest
San Diego, California, 92103, United States
UM Sylvester Comprehensive Cancer Center at Aventura
Aventura, Florida, 33180, United States
UM Sylvester Comprehensive Cancer Center at Coral Gables
Coral Gables, Florida, 33146, United States
UM Sylvester Comprehensive Cancer Center at Coral Springs
Coral Springs, Florida, 33065, United States
UM Sylvester Comprehensive Cancer Center at Deerfield Beach
Deerfield Beach, Florida, 33442, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
UM Sylvester Comprehensive Cancer Center at Kendall
Miami, Florida, 33176, United States
UM Sylvester Comprehensive Cancer Center at Plantation
Plantation, Florida, 33324, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, 83706, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, 83605, United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, 83814, United States
Saint Luke's Cancer Institute - Fruitland
Fruitland, Idaho, 83619, United States
Saint Luke's Cancer Institute - Meridian
Meridian, Idaho, 83642, United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, 83687, United States
Saint Luke's Cancer Institute - Nampa
Nampa, Idaho, 83687, United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho, 83854, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, 83864, United States
SIH Cancer Institute
Carterville, Illinois, 62918, United States
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612, United States
University of Illinois
Chicago, Illinois, 60612, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois, 62526, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, 60201, United States
NorthShore University HealthSystem-Glenbrook Hospital
Glenview, Illinois, 60026, United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park, Illinois, 60035, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Carle BroMenn Medical Center
Normal, Illinois, 61761, United States
Carle Cancer Institute Normal
Normal, Illinois, 61761, United States
Cancer Care Center of O'Fallon
O'Fallon, Illinois, 62269, United States
Mercyhealth Cancer Institute - Rockford
Rockford, Illinois, 61114, United States
Southern Illinois University School of Medicine
Springfield, Illinois, 62702, United States
Springfield Clinic
Springfield, Illinois, 62702, United States
Springfield Memorial Hospital
Springfield, Illinois, 62781, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
Woodland Cancer Care Center
Michigan City, Indiana, 46360, United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa, 50023, United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa, 50309, United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa, 50314, United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa, 50263, United States
Saint Joseph Hospital East
Lexington, Kentucky, 40509, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Harold Alfond Center for Cancer Care
Augusta, Maine, 04330, United States
Lafayette Family Cancer Center-EMMC
Brewer, Maine, 04412, United States
MaineHealth Maine Medical Center- Scarborough
Scarborough, Maine, 04074, United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Walter Reed National Military Medical Center
Bethesda, Maryland, 20889-5600, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
UPMC Western Maryland
Cumberland, Maryland, 21502, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan, 48188, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan, 48118, United States
Corewell Health Dearborn Hospital
Dearborn, Michigan, 48124, United States
OSF Saint Francis Hospital and Medical Group
Escanaba, Michigan, 49829, United States
Corewell Health Farmington Hills Hospital
Farmington Hills, Michigan, 48336, United States
Cancer Hematology Centers - Flint
Flint, Michigan, 48503, United States
Genesee Hematology Oncology PC
Flint, Michigan, 48503, United States
Genesys Hurley Cancer Institute
Flint, Michigan, 48503, United States
Hurley Medical Center
Flint, Michigan, 48503, United States
University of Michigan Health - Sparrow Lansing
Lansing, Michigan, 48912, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154, United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan, 48341, United States
Corewell Health William Beaumont University Hospital
Royal Oak, Michigan, 48073, United States
Corewell Health Beaumont Troy Hospital
Troy, Michigan, 48085, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197, United States
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota, 56601, United States
Essentia Health - Deer River Clinic
Deer River, Minnesota, 56636, United States
Essentia Health Cancer Center
Duluth, Minnesota, 55805, United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota, 55746, United States
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Essentia Health Sandstone
Sandstone, Minnesota, 55072, United States
Essentia Health Virginia Clinic
Virginia, Minnesota, 55792, United States
Saint Francis Medical Center
Cape Girardeau, Missouri, 63703, United States
Community Hospital of Anaconda
Anaconda, Montana, 59711, United States
Billings Clinic Cancer Center
Billings, Montana, 59101, United States
Bozeman Health Deaconess Hospital
Bozeman, Montana, 59715, United States
Benefis Sletten Cancer Institute
Great Falls, Montana, 59405, United States
Logan Health Medical Center
Kalispell, Montana, 59901, United States
Community Medical Center
Missoula, Montana, 59804, United States
OptumCare Cancer Care at Seven Hills
Henderson, Nevada, 89052, United States
OptumCare Cancer Care at Charleston
Las Vegas, Nevada, 89102, United States
OptumCare Cancer Care at Fort Apache
Las Vegas, Nevada, 89148, United States
Jersey City Medical Center
Jersey City, New Jersey, 07302, United States
Monmouth Medical Center Southern Campus
Lakewood, New Jersey, 08701, United States
Monmouth Medical Center
Long Branch, New Jersey, 07740, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
Community Medical Center
Toms River, New Jersey, 08755, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Cone Health MedCenter Asheboro
Asheboro, North Carolina, 27205, United States
Cone Health Cancer Center at Alamance Regional
Burlington, North Carolina, 27215, United States
Southeastern Medical Oncology Center-Clinton
Clinton, North Carolina, 28328, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Southeastern Medical Oncology Center-Goldsboro
Goldsboro, North Carolina, 27534, United States
Cone Health Cancer Center
Greensboro, North Carolina, 27403, United States
Cone Health Cancer Center at Drawbridge Parkway
Greensboro, North Carolina, 27410, United States
Southeastern Medical Oncology Center-Jacksonville
Jacksonville, North Carolina, 28546, United States
Duke Women's Cancer Care Raleigh
Raleigh, North Carolina, 27607, United States
Annie Penn Memorial Hospital
Reidsville, North Carolina, 27320, United States
Sanford Bismarck Medical Center
Bismarck, North Dakota, 58501, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
OhioHealth O'Bleness Hospital
Athens, Ohio, 45701, United States
Miami Valley Hospital South
Centerville, Ohio, 45459, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Columbus Oncology and Hematology Associates Inc
Columbus, Ohio, 43214, United States
Riverside Methodist Hospital
Columbus, Ohio, 43214, United States
Grant Medical Center
Columbus, Ohio, 43215, United States
Doctors Hospital
Columbus, Ohio, 43228, United States
Miami Valley Hospital
Dayton, Ohio, 45409, United States
Premier Blood and Cancer Center
Dayton, Ohio, 45409, United States
Dayton Physician LLC - Englewood
Dayton, Ohio, 45415, United States
Miami Valley Hospital North
Dayton, Ohio, 45415, United States
Delaware Health Center-Grady Cancer Center
Delaware, Ohio, 43015, United States
Grady Memorial Hospital
Delaware, Ohio, 43015, United States
Columbus Oncology and Hematology Associates
Dublin, Ohio, 43016, United States
Dublin Methodist Hospital
Dublin, Ohio, 43016, United States
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066, United States
Miami Valley Cancer Care and Infusion
Greenville, Ohio, 45331, United States
Kettering Medical Center
Kettering, Ohio, 45429, United States
OhioHealth Mansfield Hospital
Mansfield, Ohio, 44903, United States
OhioHealth Marion General Hospital
Marion, Ohio, 43302, United States
OhioHealth Pickerington Methodist Hospital
Pickerington, Ohio, 43147, United States
Upper Valley Medical Center
Troy, Ohio, 45373, United States
OhioHealth Westerville Medical Campus/Westerville Cancer Center
Westerville, Ohio, 43082, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Saint Alphonsus Cancer Care Center-Ontario
Ontario, Oregon, 97914, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Providence Saint Vincent Medical Center
Portland, Oregon, 97225, United States
UPMC Altoona
Altoona, Pennsylvania, 16601, United States
UPMC Hillman Cancer Center Erie
Erie, Pennsylvania, 16505, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, 15601, United States
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion
Mechanicsburg, Pennsylvania, 17050, United States
UPMC Hillman Cancer Center - Monroeville
Monroeville, Pennsylvania, 15146, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
UPMC-Magee Womens Hospital
Pittsburgh, Pennsylvania, 15213, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
UPMC-Passavant Hospital
Pittsburgh, Pennsylvania, 15237, United States
Asplundh Cancer Pavilion
Willow Grove, Pennsylvania, 19090, United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
Bristol Regional Medical Center
Bristol, Tennessee, 37620, United States
Regional Cancer Center at Johnson City Medical Center
Johnson City, Tennessee, 37604, United States
Ballad Health Cancer Care - Kingsport
Kingsport, Tennessee, 37660, United States
Wellmont Holston Valley Hospital and Medical Center
Kingsport, Tennessee, 37660, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Scott and White Memorial Hospital
Temple, Texas, 76508, United States
Ballad Health Cancer Care - Bristol
Bristol, Virginia, 24201, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
Inova Schar Cancer Institute
Fairfax, Virginia, 22031, United States
Inova Fairfax Hospital
Falls Church, Virginia, 22042, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
Swedish Cancer Institute-Edmonds
Edmonds, Washington, 98026, United States
Swedish Cancer Institute-Issaquah
Issaquah, Washington, 98029, United States
Swedish Medical Center-First Hill
Seattle, Washington, 98122, United States
West Virginia University Healthcare
Morgantown, West Virginia, 26506, United States
Duluth Clinic Ashland
Ashland, Wisconsin, 54806, United States
Marshfield Medical Center-EC Cancer Center
Eau Claire, Wisconsin, 54701, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303, United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin, 54601, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Marshfield Medical Center - Minocqua
Minocqua, Wisconsin, 54548, United States
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017, United States
Saint Vincent Hospital Cancer Center at Oconto Falls
Oconto Falls, Wisconsin, 54154, United States
Marshfield Medical Center-Rice Lake
Rice Lake, Wisconsin, 54868, United States
Saint Vincent Hospital Cancer Center at Sheboygan
Sheboygan, Wisconsin, 53081, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point, Wisconsin, 54482, United States
Saint Vincent Hospital Cancer Center at Sturgeon Bay
Sturgeon Bay, Wisconsin, 54235-1495, United States
Marshfield Medical Center - Weston
Weston, Wisconsin, 54476, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Haider S Mahdi
NRG Oncology
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 9, 2023
First Posted
November 13, 2023
Study Start
May 7, 2024
Primary Completion (Estimated)
February 20, 2027
Study Completion (Estimated)
February 20, 2027
Last Updated
April 16, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
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