Phase II Study of Ramucirumab With Trastuzumab, Fluoropyrimidine, and Platinum in Patients With Metastatic HER2-Positive Gastroesophageal Junction and Gastric Cancer
Overview
- Phase
- Phase 2
- Intervention
- Ramucirumab
- Conditions
- Gastric Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 7
- Locations
- 6
- Primary Endpoint
- Progression Free Survival
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
The purpose of this study is to compare any good and bad effects of using ramucirumab along with the usual trastuzumab and chemotherapy to using the usual chemotherapy and trastuzumab alone.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have pathologically or cytologically MSKCC confirmed diagnosis of gastric or GEJ adenocarcinoma.
- •Patients must have Stage IV gastric or GEJ adenocarcinoma with HER2 overexpression and/or amplification as determined by next generation sequencing assay, immunohistochemistry (IHC 3+) or fluorescent in situ hybridization (FISH+ is defined as HER2:CEP17 ratio ≥ 2.0). MSKCC confirmation of HER2 status is not mandatory prior to enrollment and treatment on study. For patients with outside HER2 testing, if sufficient tissue is available HER2 testing will be repeated at MSKCC for purpose of analysis and will not impact the patient's eligibility.
- •Available archival tumor tissue should be submitted to MSKCC for IMPACT analysis, but will not be required prior to registration. Note: if tissue is depleted, patient will still be eligible after discussion with the PI.
- •Patients must have disease that can be evaluated radiographically. This may be measurable disease or non-measurable disease per RECIST 1.
- •Patients may have received no prior chemotherapy for Stage IV disease. Patients may have received prior adjuvant therapy (chemotherapy and/or chemoradiation) if more than 6 months have elapsed between the end of adjuvant therapy and registration.
- •Age of 18 years or older.
- •ECOG performance status 0-
- •Peripheral neuropathy ≤ grade 1
- •Patients who have adequate hepatic function as defined by a total bilirubin ≤1.5 times upper limit of institutional normal value (ULN) mg/dL (except patients with Gilbert's disease), and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times ULN or ≤ 5.0 times the ULN in the setting of liver metastases.
- •Patients who have adequate hematologic function, as evidenced by absolute neutrophil count (ANC) ≥1500/μL, hemoglobin ≥9 g/dL (5.58 mmol/L), and platelets ≥100,000/μL.
Exclusion Criteria
- •Patients who have uncontrolled or poorly-controlled hypertension (\>160 mmHg systolic or \>100 mmHg diastolic for \>4 weeks) despite standard medical management.
- •Patients receiving any concurrent anticancer therapy or investigational agents with the intention of treating gastric/GEJ cancer. Previously received trastuzumab as part of a regimen in the metastatic setting with evidence of progression. 89Zr-trastuzumab use as imaging agent for 89Zr-trastuzumab PET permitted.
- •Patients having:
- •Cirrhosis at a level of Child-Pugh B (or worse) or
- •Cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
- •Active or clinically significant cardiac disease including:
- •Congestive heart failure - New York Heart Association (NYHA) \> Class II.
- •Active coronary artery disease.
- •Left ventricular function \<50%.
- •Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
Arms & Interventions
Ramucirumab With Trastuzumab and Capecitabine/Cisplatin
This will be a single arm study of ramucirumab 8mg/kg administered intravenously on days 1 and 8 + trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) administered intravenously every 21 days. On subsequent cycles for all patients capecitabine 850mg/m2 will be added, taken orally twice a day for fourteen days (days 1 through 14) followed by a 7 day rest period, in addition to cisplatin 80mg/m2 administered as an IV infusion every 21 days. Each cycle consists of 21 days.
Intervention: Ramucirumab
Ramucirumab With Trastuzumab and Capecitabine/Cisplatin
This will be a single arm study of ramucirumab 8mg/kg administered intravenously on days 1 and 8 + trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) administered intravenously every 21 days. On subsequent cycles for all patients capecitabine 850mg/m2 will be added, taken orally twice a day for fourteen days (days 1 through 14) followed by a 7 day rest period, in addition to cisplatin 80mg/m2 administered as an IV infusion every 21 days. Each cycle consists of 21 days.
Intervention: Trastuzumab
Ramucirumab With Trastuzumab and Capecitabine/Cisplatin
This will be a single arm study of ramucirumab 8mg/kg administered intravenously on days 1 and 8 + trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) administered intravenously every 21 days. On subsequent cycles for all patients capecitabine 850mg/m2 will be added, taken orally twice a day for fourteen days (days 1 through 14) followed by a 7 day rest period, in addition to cisplatin 80mg/m2 administered as an IV infusion every 21 days. Each cycle consists of 21 days.
Intervention: Capecitabine
Ramucirumab With Trastuzumab and Capecitabine/Cisplatin
This will be a single arm study of ramucirumab 8mg/kg administered intravenously on days 1 and 8 + trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) administered intravenously every 21 days. On subsequent cycles for all patients capecitabine 850mg/m2 will be added, taken orally twice a day for fourteen days (days 1 through 14) followed by a 7 day rest period, in addition to cisplatin 80mg/m2 administered as an IV infusion every 21 days. Each cycle consists of 21 days.
Intervention: Cisplatin
Outcomes
Primary Outcomes
Progression Free Survival
Time Frame: 6 months
as measured from the start of the ramucirumab and trastuzumab to the date of either documentation of disease progression on chemotherapy with trastuzumab and ramucirumab or death.