This study is currently recruiting participants.
Number
002090-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Pregnant Women
Keywords
Solid Tumor; Targeted Therapy
Recruitment Keyword(s)
None
Condition(s)
HER2 positive cancers
Investigational Drug(s)
Neratinib Palbociclib
Investigational Device(s)
Intervention(s)
Drug: neratinib Drug: Palbociclib
Supporting Site
National Cancer Institute
Human growth factor receptor 2 (HER2) is a protein that has been linked to several cancers. These include tumors in the breast, uterus, lungs, and colon. Treatments that target HER2 have been found to be effective against some cancers with HER2. Researchers want to find out if these treatments also work against other types of tumors with HER2.
Objective:
To test a drug (neratinib), alone and combined with another drug (palbociclib), in people with cancers that have HER2.
Eligibility:
People aged 18 years and older with cancer (except of the breast) that has the HER2 protein. Participants must be enrolled in the ComboMATCH Master Registration Trial EAY191.
Design:
Participants will be screened. They will have imaging scans and tests of their heart function. Small samples of tumor tissue will be collected. Blood and tissue samples will be used for genetic testing.
Neratinib and palbociclib are both pills taken by mouth once a day. Half of participants will take only neratinib; the other half will take both drugs. Treatment will be in 28-day cycles.
All participants will begin with gradually increasing doses of neratinib for 14 days; then they will take the full dosage every day of each 28-day cycle.
Those taking both drugs will take palbociclib every day for 3 weeks, followed by 1 week with no drugs, during each 28-day cycle.
Participants may remain in the study as long as the treatment is helping them.
Follow-up checks will continue up to 2 years after treatment ends.
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ELIGIBILITY CRITERIA: A patient cannot be considered eligible for this study unless ALL of the following conditions are met. 1. Patients must be enrolled on the ComboMATCH Master Registration Trial EAY191. 2. Documentation of Disease -Patients must have a HER2 amplified solid tumor except breast cancer. Patient s cancer must have HER2 amplification as defined with >= 7 copies by NGS testing. -Patients must have recurrent or persistent disease. -No known evidence of RB1 loss or deletion including copy number loss or deleterious mutation. 3. 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). 4. Definition of Measurable Disease as defined by RECIST -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 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. 5. Prior Treatment -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 TDM1. -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. 6. Age >= 18 7. ECOG Performance Status of <=2 8. Not Pregnant and Not Nursing 9. Required Organ Function Adequate hematologic function defined as follows: -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 Hgb >=9 g/dl is acceptable). Adequate renal function defined as follows: -Creatinine clearance (CrCL) of >=30 mL/min by the Cockcroft-Gault formula CrCl (mL/min) = [140 - age (years)] x weight (kg)/72 x creatinine (mg / dL) {x 0.85 for female patients} Adequate hepatic function defined as follows: -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). -AST and ALT <= 3 x institutional ULN. Adequate cardiac function defined as follows: -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 10. Comorbid Conditions -No active infection requiring parenteral antibiotics -No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, 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 11. Allergies -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
A patient cannot be considered eligible for this study unless ALL of the following conditions are met.
1. Patients must be enrolled on the ComboMATCH Master Registration Trial EAY191.
2. Documentation of Disease
-Patients must have a HER2 amplified solid tumor except breast cancer. Patient s cancer must have HER2 amplification as defined with >= 7 copies by NGS testing.
-Patients must have recurrent or persistent disease.
-No known evidence of RB1 loss or deletion including copy number loss or deleterious mutation.
3. 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).
4. Definition of Measurable Disease as defined by RECIST
-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 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.
5. Prior Treatment
-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 TDM1.
-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.
6. Age >= 18
7. ECOG Performance Status of <=2
8. Not Pregnant and Not Nursing
9. Required Organ Function
Adequate hematologic function defined as follows:
-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 Hgb >=9 g/dl is acceptable).
Adequate renal function defined as follows:
-Creatinine clearance (CrCL) of >=30 mL/min by the Cockcroft-Gault formula
CrCl (mL/min) = [140 - age (years)] x weight (kg)/72 x creatinine (mg / dL) {x 0.85 for female patients}
Adequate hepatic function defined as follows:
-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).
-AST and ALT <= 3 x institutional ULN.
Adequate cardiac function defined as follows:
-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
10. Comorbid Conditions
-No active infection requiring parenteral antibiotics
-No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, 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
11. Allergies
-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
Principal Investigator
Referral Contact
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