Testing Trastuzumab and Pertuzumab in Patients With Higher Than Normal Copies of the HER2 Gene Found in Their Tumors (MATCH - Subprotocol J)

Study Overview
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Brief Summary
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This phase II MATCH treatment trial tests how well trastuzumab and pertuzumab work in treating patients with HER2-amplified non-breast, non-gastric/gastroesophageal junction, and non-colorectal cancers. Pertuzumab and trastuzumab are monoclonal antibodies and forms of targeted therapy that attach to a receptor protein called HER2. HER2 is found on some cancer cells. When pertuzumab or trastuzumab attach to HER2, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Trastuzumab is approved for the treatment of certain types of HER2-amplified cancers such as breast and gastric cancers. Research has shown that treatment with two anti-HER2 therapies in combination may be more effective at treating HER2-positive patients than giving one anti-HER2 therapy alone. Giving trastuzumab and pertuzumab in combination may be effective at treating patients with HER2-amplified cancers that aren't breast, gastric, or colorectal.

Detailed Description
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PRIMARY OBJECTIVE: I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma. SECONDARY OBJECTIVES: I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma. II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms. IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens. OUTLINE: Patients receive pertuzumab intravenously (IV) over 30-60 minutes and trastuzumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, echocardiography (ECHO) at screening and end of treatment, and biopsy and collection of blood samples on trial and at end of treatment. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.

Official Title
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Trastuzumab and Pertuzumab (HP) in Patients With Non-Breast, Non-Gastric/GEJ, and Non-Colorectal Cancers With HER2 Amplification

Conditions
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Malignant Solid Neoplasm

Intervention / Treatment
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* Procedure: Biopsy
* Procedure: Biospecimen Collection
* Procedure: Echocardiography
* Biological: Pertuzumab
* Procedure: Radiologic Examination
* Biological: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol Patients must fulfill all eligibility criteria outlined the MATCH Master Protocol at the time of registration to treatment step (step 1, 3, 5, 7) Patients must have HER2 amplification, or another aberration, as determined via the MATCH Master Protocol Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block) Patients must have ECHO or multigated acquisition scan (MUGA) within 4 weeks prior to treatment assignment and must not have a left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be >= 50% for the patient to be eligible Patients must not have breast cancer, gastric/gastroesophageal junction (GEJ)/esophageal adenocarcinoma or mixed histology, gastric/GEJ not otherwise specified (NOS) tumors, or colorectal adenocarcinoma Patients must not have known hypersensitivity to trastuzumab or pertuzumab or compounds of similar chemical or biologic composition Patients must not have received prior anti-HER2 therapies, including trastuzumab, pertuzumab, trastuzumab emtansine (T-DM1), lapatinib, afatinib, neratinib, dacomitinib, canertinib Women of childbearing potential (WOCBP) and men who are sexually active with WOCBP must agree to use adequate contraception (hormonal or double barrier method of birth control, abstinence) from one week prior to study treatment starting, during treatment, and for a period of 7 months after the last dose of study treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (pertuzumab, trastuzumab)<br>Patients receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO at screening and end of treatment, and biopsy and collection of blood samples on trial and at end of treatment. | Procedure: Biopsy<br>* Undergo biopsy<br>* Other names: Bx;Procedure: Biospecimen Collection<br>* Undergo collection of blood samples<br>* Other names: Specimen Collection;Procedure: Echocardiography<br>* Undergo ECHO<br>* Other names: EC;Biological: Pertuzumab<br>* Given IV<br>* Other names: TQB2440;Procedure: Radiologic Examination<br>* Undergo radiologic evaluation<br>* Other names: Radiologic Exam;Biological: Trastuzumab<br>* Given IV<br>* Other names: Trazimera;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | Defined as the percentage of patients whose tumors have a complete or partial response to treatment. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria. 90% two-sided confidence intervals will be calculated. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Estimated using the Kaplan-Meier method. | From registration until death, assessed up to 3 years | 
| Progression free survival | Estimated using the Kaplan-Meier method. 90% two-sided confidence intervals will be calculated. | From registration until determination of disease progression or death from any cause, assessed at 6 months |