Phase II Trial of Pembrolizumab in Combination With Trastuzumab, Fluoropyrimidine, and Platinum Chemotherapy in First Line Stage IV HER2-positive Metastatic Esophagogastric (EG) Cancer
Overview
- Phase
- Phase 2
- Intervention
- pembrolizumab
- Conditions
- Esophageal Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 37
- Locations
- 8
- Primary Endpoint
- Percentage of Participants With Progression Free Survival
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to find out what effects, good and/or bad, pembrolizumab in combination with trastuzumab and chemotherapy, has on the patients' esophagogastric cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient must have pathologically or cytologically MSKCC confirmed esophageal, gastric or gastroesophageal junction (GEJ) adenocarcinoma by the enrolling institution.
- •Patients must have esophageal, gastric or gastroesophageal 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 or enrolling institution 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 or enrolling institution for purpose of analysis and will not impact the patient's eligibility.
- •Additional available archival tumor tissue in the form of 15-20 unstained slides should be submitted to MSKCC for future correlative analysis, but will not be required prior registration. Note: if tissue is depleted, patient will still be eligible after discussion with the MSK PI.
- •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
- •Patients must have disease that can be evaluated radiographically. This may be measurable disease or non-measurable disease per RECIST 1.
- •Patient must have a normal LVEF (\>/= 53%). If a patient has a borderline LVEF (40-52%) they may be considered after consultation with cardiology and study PI and treated per the guidelines in section 11.2.
- •Age 18 years or older.
- •ECOG performance status 0-
- •Demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days of treatment initiation.
- •Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L Renal Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (measured via 24-hour urine collection) ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl) Hepatic Serum total bilirubin ≤ 1.5 X ULN (1.5 mg/dL or 25.65 μmol/L) OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN. Except patients with Gilbert's disease (≤3x ULN) AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR AST (SGOT) and ALT (SGPT) ≤ 5 X ULN for subjects with liver metastases Albumin \>2.5 mg/dL Coagulation Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
Exclusion Criteria
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has a known history of active TB (Bacillus tuberculosis)
- •Hypersensitivity to pembrolizumab or any of its excipients.
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. (Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.)
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has known history of, or any evidence of active, non-infectious pneumonitis.
- •Has an active infection requiring systemic therapy.
- •Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Arms & Interventions
Pembrolizumab, trastuzumab,capecitabine/cisplatin
Pembrolizumab 200 mg IV every 3 weeks, trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) IV every 3 weeks with cisplatin IV every 3 weeks with oral capecitabine 2 weeks on/1 week off. Each cycle consists of 21 days. Treatment will be administered on an outpatient basis. In Cycle 1, patients will initiate therapy with trastuzumab 8 mg/kg IV with pembrolizumab 200 mg IV. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to pembrolizumab and trastuzumab combination. With subsequent cycles, all patients will begin systemic chemotherapy with the capecitabine/cisplatin regimen in addition to pembrolizumab 200 mg IV with trastuzumab 6 mg/kg maintenance. Patients will receive cisplatin 80 mg/m2 IV on Day 1, and capecitabine 850mg/m2 twice a day on Days 1 through 14, every 3 weeks.
Intervention: pembrolizumab
Pembrolizumab, trastuzumab,capecitabine/cisplatin
Pembrolizumab 200 mg IV every 3 weeks, trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) IV every 3 weeks with cisplatin IV every 3 weeks with oral capecitabine 2 weeks on/1 week off. Each cycle consists of 21 days. Treatment will be administered on an outpatient basis. In Cycle 1, patients will initiate therapy with trastuzumab 8 mg/kg IV with pembrolizumab 200 mg IV. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to pembrolizumab and trastuzumab combination. With subsequent cycles, all patients will begin systemic chemotherapy with the capecitabine/cisplatin regimen in addition to pembrolizumab 200 mg IV with trastuzumab 6 mg/kg maintenance. Patients will receive cisplatin 80 mg/m2 IV on Day 1, and capecitabine 850mg/m2 twice a day on Days 1 through 14, every 3 weeks.
Intervention: trastuzumab
Pembrolizumab, trastuzumab,capecitabine/cisplatin
Pembrolizumab 200 mg IV every 3 weeks, trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) IV every 3 weeks with cisplatin IV every 3 weeks with oral capecitabine 2 weeks on/1 week off. Each cycle consists of 21 days. Treatment will be administered on an outpatient basis. In Cycle 1, patients will initiate therapy with trastuzumab 8 mg/kg IV with pembrolizumab 200 mg IV. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to pembrolizumab and trastuzumab combination. With subsequent cycles, all patients will begin systemic chemotherapy with the capecitabine/cisplatin regimen in addition to pembrolizumab 200 mg IV with trastuzumab 6 mg/kg maintenance. Patients will receive cisplatin 80 mg/m2 IV on Day 1, and capecitabine 850mg/m2 twice a day on Days 1 through 14, every 3 weeks.
Intervention: capecitabine
Pembrolizumab, trastuzumab,capecitabine/cisplatin
Pembrolizumab 200 mg IV every 3 weeks, trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) IV every 3 weeks with cisplatin IV every 3 weeks with oral capecitabine 2 weeks on/1 week off. Each cycle consists of 21 days. Treatment will be administered on an outpatient basis. In Cycle 1, patients will initiate therapy with trastuzumab 8 mg/kg IV with pembrolizumab 200 mg IV. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to pembrolizumab and trastuzumab combination. With subsequent cycles, all patients will begin systemic chemotherapy with the capecitabine/cisplatin regimen in addition to pembrolizumab 200 mg IV with trastuzumab 6 mg/kg maintenance. Patients will receive cisplatin 80 mg/m2 IV on Day 1, and capecitabine 850mg/m2 twice a day on Days 1 through 14, every 3 weeks.
Intervention: cisplatin
Pembrolizumab, trastuzumab,capecitabine/cisplatin
Pembrolizumab 200 mg IV every 3 weeks, trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) IV every 3 weeks with cisplatin IV every 3 weeks with oral capecitabine 2 weeks on/1 week off. Each cycle consists of 21 days. Treatment will be administered on an outpatient basis. In Cycle 1, patients will initiate therapy with trastuzumab 8 mg/kg IV with pembrolizumab 200 mg IV. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to pembrolizumab and trastuzumab combination. With subsequent cycles, all patients will begin systemic chemotherapy with the capecitabine/cisplatin regimen in addition to pembrolizumab 200 mg IV with trastuzumab 6 mg/kg maintenance. Patients will receive cisplatin 80 mg/m2 IV on Day 1, and capecitabine 850mg/m2 twice a day on Days 1 through 14, every 3 weeks.
Intervention: Oxaliplatin
Pembrolizumab, trastuzumab,capecitabine/cisplatin
Pembrolizumab 200 mg IV every 3 weeks, trastuzumab (8 mg/kg loading dose; 6 mg/kg maintenance) IV every 3 weeks with cisplatin IV every 3 weeks with oral capecitabine 2 weeks on/1 week off. Each cycle consists of 21 days. Treatment will be administered on an outpatient basis. In Cycle 1, patients will initiate therapy with trastuzumab 8 mg/kg IV with pembrolizumab 200 mg IV. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to pembrolizumab and trastuzumab combination. With subsequent cycles, all patients will begin systemic chemotherapy with the capecitabine/cisplatin regimen in addition to pembrolizumab 200 mg IV with trastuzumab 6 mg/kg maintenance. Patients will receive cisplatin 80 mg/m2 IV on Day 1, and capecitabine 850mg/m2 twice a day on Days 1 through 14, every 3 weeks.
Intervention: 5-Fluorouracil
Outcomes
Primary Outcomes
Percentage of Participants With Progression Free Survival
Time Frame: 6 months
We will define progression of disease per RECIST 1.1 criteria