Testing neratinib alone or with palbociclib for HER2 positive solid tumors

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase II trial evaluates the effectiveness of neratinib compared to a combination of neratinib and palbociclib in patients with HER2 positive solid tumors, particularly focusing on gynecologic cancers. The study aims to assess progression-free survival, objective response rates, and overall survival while monitoring adverse events. Patients will undergo biopsies and imaging tests to gather data on treatment response and tumor characteristics. The trial also explores the relationship between circulating tumor DNA and tumor tissue profiles to better understand treatment efficacy.

Why it matters

Who can join: the full rules

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.

  * 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
* Prior therapy with trastuzumab or pertuzumab, either alone or in combination, antibody drug conjugates (ADC) such as DS8201a or T-DM1 is allowed
* No prior therapy with HER2 targeting tyrosine kinase inhibitors (TKI) such as neratinib or tucatinib
* 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. No HER2 targeting ADCs within 30 days prior to registration
* 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

Where it's running

• University of Alabama at Birmingham Cancer Center
  Birmingham, Alabama, United States Recruiting
• University of South Alabama Mitchell Cancer Institute
  Mobile, Alabama, United States Recruiting
• Alaska Women's Cancer Care
  Anchorage, Alaska, United States Recruiting
• UC San Diego Health System - Encinitas
  Encinitas, California, United States Recruiting
• UC San Diego Moores Cancer Center
  La Jolla, California, United States Recruiting
• The Angeles Clinic and Research Institute - West Los Angeles Office
  Los Angeles, California, United States Recruiting

+144 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Principal investigator: Haider S Mahdi — NRG Oncology

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Targeted therapy for advanced solid tumors based on genetic testing

  This study is testing whether matching patients with advanced solid tumors to specific treatments based on their genetic makeup can improve their outcomes when standard options have failed.

  Recruiting at 437 sites Phase 2 National Cancer Institute (NCI) · Birmingham, Alabama and 483 other locations · NCT05564377

• Using fucoidan to prevent fatigue in cancer patients undergoing chemotherapy

  This study tests if a seaweed supplement called fucoidan can help cancer patients undergoing chemotherapy feel less tired.

  Recruiting Phase 2 Mayo Clinic · Scottsdale, Arizona · NCT06855524

• Genetic testing for cancer in diverse ethnic groups

  This study is testing how genetic testing can help cancer patients from different ethnic backgrounds understand their risks and improve their personalized care.

  Recruiting at 2 sites Mayo Clinic · Scottsdale, Arizona and 1 other locations · NCT04475640

• Collecting and storing tissue and blood samples from cancer patients

  This study is collecting and storing blood and tissue samples from cancer patients to help researchers create better models for understanding cancer and testing new treatments.

  Recruiting at 18 sites National Cancer Institute (NCI) · Birmingham, Alabama and 139 other locations · NCT02474160

• See if virtual informed consent methods help people decide to join cancer research

  This trial tests whether virtual human communicators and different consent messages can influence cancer patients’ understanding and willingness to participate in research.

  Recruiting Mayo Clinic · Jacksonville, Florida · NCT07805083

• AI-powered supportive care chatbot for young adult cancer survivors

  A chatbot driven by artificial intelligence is tested to help young adult cancer survivors manage symptoms and care needs after treatment.

  Recruiting University of Michigan Rogel Cancer Center · Ann Arbor, Michigan · NCT07772596

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.