Clinical Trials /

Phase II Study of Ramucirumab With Chemotherapy in Patients With Metastatic Gastroesophageal Junction and Gastric Cancer

NCT02726399

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ramucirumab</span> With <span class="go-doc-concept go-doc-intervention">Trastuzumab</span> and <span class="go-doc-concept go-doc-intervention">Capecitabine</span>/<span class="go-doc-concept go-doc-intervention">Cisplatin</span> in Patients With Metastatic <span class="go-doc-concept go-doc-biomarker">HER2</span>-Positive Gastroesophageal Junction and Gastric Cancer

Title

  • Brief Title: Ramucirumab With Trastuzumab and Capecitabine/Cisplatin in Patients With Metastatic HER2-Positive Gastroesophageal Junction and Gastric Cancer
  • Official Title: Phase II Study of Ramucirumab With Trastuzumab and Capecitabine/Cisplatin in Patients With Metastatic HER2-Positive Gastroesophageal Junction and Gastric Cancer
  • Clinical Trial IDs

    NCT ID: NCT02726399

    ORG ID: 15-301

    Trial Conditions

    Gastric Cancer

    Gastroesophageal Junction Cancer

    Trial Interventions

    Drug Synonyms Arms
    Ramucirumab Ramucirumab With Trastuzumab and Capecitabine/Cisplatin
    Trastuzumab Ramucirumab With Trastuzumab and Capecitabine/Cisplatin
    Capecitabine/Cisplatin Ramucirumab With Trastuzumab and Capecitabine/Cisplatin

    Trial Purpose

    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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Ramucirumab With Trastuzumab and Capecitabine/Cisplatin Experimental 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. CT/MRI scan will be performed after the initial 3 weeks (1 cycle) to determine response to ramucirumab with trastuzumab, and every 9 weeks thereafter. 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. Ramucirumab, Trastuzumab, Capecitabine/Cisplatin

    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 1.1.

    - 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 0-1.

    - 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/L, hemoglobin 9 g/dL (5.58 mmol/L), and platelets 100,000/L.

    - Patients who have adequate renal function as defined by calculated creatinine
    clearance 60 mL/minute using the Cockcroft-Gaul formula or equivalent method.

    - Patients whose urinary protein is 2+ on routine urinalysis (UA; if routine analysis
    is >2+, a 24-hour urine collection for protein must demonstrate <2g of protein in 24
    hours to allow participation in this protocol).

    - Patients must have adequate coagulation function as defined by International
    Normalized Ratio (INR) 1.5 and a partial thromboplastin time (PTT) 5 seconds above
    the ULN (unless receiving anticoagulation therapy). Patients on full-dose
    anticoagulation must be on a stable dose (minimum duration 14 days) of oral
    anticoagulant or low molecular weight heparin. Patients receiving warfarin must be
    switched to low molecular weight heparin and have achieved stable coagulation profile
    prior to randomization.

    - Patients, must be postmenopausal, surgically sterile, or using effective
    contraception (hormonal or barrier methods).

    - Female patients of childbearing potential must have a negative serum pregnancy test
    within 2 weeks of study entry.

    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.

    - Unstable angina (anginal symptoms at rest), new-onset angina within 3 months
    before randomization, or myocardial infarction within 6 months before
    randomization.

    - Patients who have experienced any arterial thromboembolic events, including but
    not limited to myocardial infarction, transient ischemic attack, cerebrovascular
    accident, or unstable angina, within 6 months prior to enrollment.

    - Patients who are receiving chronic antiplatelet therapy, including dipyridamole
    or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325
    mg/day) is permitted.

    - Evidence or history of bleeding diathesis or coagulopathy.

    - Patients who have experienced any Grade 3-4 GI bleeding within 3 months prior to
    enrolment.

    - Unwillingness to give written informed consent, unwillingness to participate, or
    inability to comply with the protocol for the duration of the study.

    - Patients with prior trastuzumab treatment.

    - Patients with known active brain or central nervous system metastases, including
    leptomeningeal disease. Patients with treated and asymptomatic brain metastases may
    be eligible after discussion with PI.

    - Patients who are pregnant or breast-feeding.

    - Patients with a serious or nonhealing wound, ulcer, or bone fracture within 28 days
    prior to enrollment.

    - Patients may not have had major surgical procedure within 2 weeks of registration.

    - Patients who have elective or planned major surgery to be performed during the course
    of the clinical trial.

    - Patients may not have had radiation within 2 weeks of registration.

    - Patients may not have any other medical condition or reason, in that investigator's
    opinion, makes the patient unstable to participate in a clinical trial.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    progression free survival

    Secondary Outcome Measures

    Trial Keywords

    Ramucirumab

    Trastuzumab

    Capecitabine

    Cisplatin

    HER2-Positive

    15-301