Testing Trastuzumab and Pertuzumab in Patients With Higher Than Normal Copies of the HER2 Gene Found in Their Tumors (MATCH - Subprotocol J)
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVE:
- 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:
-
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.
-
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.
-
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (pertuzumab, trastuzumab) 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
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood samples
Other Names:
Procedure: Echocardiography
Undergo ECHO
Other Names:
Biological: Pertuzumab
Given IV
Other Names:
Procedure: Radiologic Examination
Undergo radiologic evaluation
Other Names:
Biological: Trastuzumab
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Objective response rate [Up to 3 years]
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.
Secondary Outcome Measures
- Overall survival [From registration until death, assessed up to 3 years]
Estimated using the Kaplan-Meier method.
- Progression free survival [From registration until determination of disease progression or death from any cause, assessed at 6 months]
Estimated using the Kaplan-Meier method. 90% two-sided confidence intervals will be calculated.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ECOG-ACRIN Cancer Research Group | Philadelphia | Pennsylvania | United States | 19103 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Roisin M Connolly, ECOG-ACRIN Cancer Research Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NCI-2023-09506
- NCI-2023-09506
- EAY131-J
- EAY131-J
- U10CA180820