Clinical Trials /

KeyLargo: Pembrolizumab + Oxaliplatin + Capecitabine in Gastric Cancer

NCT03342937

Description:

This study will be conducted in two stages: 1) safety validation and 2) dose expansion 1. Safety Validation Cohort: The first portion of the study will preliminarily establish the tolerability of the combination of pembrolizumab, oxaliplatin and capecitabine. Five (5) subjects will be enrolled and their safety data after 21 days of treatment will be reviewed before additional subjects are enrolled. Subjects on this portion of the study will only be enrolled at the Duke Cancer Institute. 2. Dose Expansion Cohort: The second portion of the study (ie. phase II) will enroll 30 subjects. In the dose expansion cohort, the first cycle will be modified to allow one week of pembrolizumab monotherapy before starting capecitabine and oxaliplatin (XELOX) chemotherapy, which will allow analysis of biomarkers related to pembrolizumab. Subjects on this portion of the study will be enrolled at the Duke Cancer institute and select external collaborating institutions. The primary objective of this trial is to describe the progression free survival (PFS) associated with the combination of pembrolizumab, oxaliplatin and capecitabine (pembrolizumab +XELOX) in all patients with previously untreated metastatic esophagogastric adenocarcinoma.

Related Conditions:
  • Esophageal Adenocarcinoma
  • Gastric Adenocarcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: KeyLargo: Pembrolizumab + Oxaliplatin + Capecitabine in Gastric Cancer
  • Official Title: A Single Arm, Phase II Study of Pembrolizumab, Oxaliplatin, and Capecitabine in the First Line Treatment of Patients With Gastro-esophageal Cancer.

Clinical Trial IDs

  • ORG STUDY ID: Pro00080566
  • NCT ID: NCT03342937

Conditions

  • Gastric Cancer
  • Esophagus Cancer

Interventions

DrugSynonymsArms
Oxaliplatin+Capecitabine+PembrolizumabOxaliplatin+Capecitabine+Pembrolizumab

Purpose

This study will be conducted in two stages: 1) safety validation and 2) dose expansion 1. Safety Validation Cohort: The first portion of the study will preliminarily establish the tolerability of the combination of pembrolizumab, oxaliplatin and capecitabine. Five (5) subjects will be enrolled and their safety data after 21 days of treatment will be reviewed before additional subjects are enrolled. Subjects on this portion of the study will only be enrolled at the Duke Cancer Institute. 2. Dose Expansion Cohort: The second portion of the study (ie. phase II) will enroll 30 subjects. In the dose expansion cohort, the first cycle will be modified to allow one week of pembrolizumab monotherapy before starting capecitabine and oxaliplatin (XELOX) chemotherapy, which will allow analysis of biomarkers related to pembrolizumab. Subjects on this portion of the study will be enrolled at the Duke Cancer institute and select external collaborating institutions. The primary objective of this trial is to describe the progression free survival (PFS) associated with the combination of pembrolizumab, oxaliplatin and capecitabine (pembrolizumab +XELOX) in all patients with previously untreated metastatic esophagogastric adenocarcinoma.

Trial Arms

NameTypeDescriptionInterventions
Oxaliplatin+Capecitabine+PembrolizumabExperimental
  • Oxaliplatin+Capecitabine+Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically and/or cytologically documented and radiographically measurable (by
             RECIST 1.1) adenocarcinoma of the esophagus or stomach (HER2-positive or negative)
             that is metastatic/recurrent and not amenable to potentially curative treatment

          -  No prior chemotherapy for metastatic/recurrent disease. Prior adjuvant or neo-adjuvant
             treatment with a fluoropyrimidine or fluoropyrimidine based regimen is allowed only if
             it is completed at least 6 months prior to the start of study drug, whether given
             alone or with radiation therapy. Patients who have received prior neo-adjuvant therapy
             (chemotherapy and/or radiation therapy) which did not contain 5-FU or capecitabine and
             have been diagnosed with metastatic disease (with no previous treatment in the
             metastatic setting) are eligible. No 6-months window is required for these patients.
             In the setting of metastatic disease requiring local palliation, only radiosensitizing
             doses of 5-FU or capecitabine monotherapy are permitted.

          -  Prior radiation therapy is permitted, provided is completed at least 28 days prior to
             the start of study drug.

          -  Age ≥ 18 years with ability to understand and willingness to provide informed consent.

          -  ECOG performance status of 0 or 1.

          -  Adequate organ and marrow function as defined below by the following:

               1. Absolute neutrophil count (ANC) ≥ 1500 µl

               2. Platelets ≥ 100,000/µl

               3. Hemoglobin (Hgb) ≥ 9 g/dL

               4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

               5. AST/ALT ≤ 2 x ULN without liver metastasis; ≤ 5 x ULN with liver metastasis

               6. Creatinine clearance ≥ 50 cc/min

        Exclusion Criteria:

          -  Prior therapy with an anti-PD-1, anti PD-L1, anti-PD-L2, anti-CD137 antibody, or
             anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) agents.

          -  Chemotherapy, targeted small molecule therapy, radiotherapy, experimental agents,
             prior therapy with anti-tumor vaccines or other immune-stimulatory antitumor agents,
             or biological cancer therapy (including monoclonal antibodies) within 14 days prior to
             the start of study drug, or not recovered (≤ grade 1 or baseline) from adverse events
             due to a previously administered agent.

          -  Known CNS metastases and/or carcinomatous meningitis. Patients with radiated or
             resected lesions are permitted, provided the lesions are fully treated and inactive,
             patients are asymptomatic, and no steroids have been administered for at least 30 days
             prior to the start of study drug.

          -  Documented history of clinically significant autoimmune disease (other than
             well-controlled hypothyroidism) or a syndrome that requires systemic steroids or
             immunosuppressive agents. Subjects with vitiligo, type I diabetes mellitus, psoriasis
             not requiring systemic treatment, or conditions not expected to recur in the absence
             of an external trigger are permitted to enroll.

          -  Receiving systemic steroid therapy or any form of immunosuppressive therapy within 1
             week prior to the start of study drug.

          -  Received a live vaccine within 4 weeks prior to the start of the study drug.

          -  Has known history of, or any evidence of active, non-infectious pneumonitis.

          -  Known history of HIV seropositivity, hepatitis C virus, acute or chronic active
             hepatitis B infection, or other serious chronic infection requiring ongoing treatment.
             Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract
             infection or chronic obstructive pulmonary disease) are eligible.

          -  Pregnant or breastfeeding

          -  Not willing to use an effective method of birth control

          -  Concurrent severe and/or uncontrolled medical conditions, which may compromise
             participation in the study, including impaired heart function or clinically
             significant heart disease.

          -  Current use of medication specified by the protocol as prohibited for administration
             in combination with the study drug. This includes patients with a condition requiring
             systemic treatment with either corticosteroids (>10mg daily prednisone equivalents) or
             other immunosuppressive medications within 14 days prior to the start of study drug.
             Inhaled or topical steroids and adrenal replacement doses > 10mg daily prednisone
             equivalents are permitted in the absence of active autoimmune disease.

          -  Recent or current active infectious disease requiring systemic antibiotics,
             antifungal, or antiviral treatment within 2 weeks prior to the start of study drug.

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to the start of study drug (56 days for hepatectomy, open thoracotomy, major
             neurosurgery) or anticipation of need for major surgical procedure during the course
             of the study (except fot rhe planned metastatectomy).

          -  Serious, non-healing wound, ulcer, or bone fracture.

          -  History of myocardial infarction, NYHA lass III or IV congestive heart failure,
             arrhythmia requiring therapy, unstable angina, cardia or other vascular stenting,
             angioplasty, or surgery within 6 months prior to the start of study drug.

          -  History of other carcinomas within the last five years, except cured non-melanoma skin
             cancer, curatively treated in-situ cervical cancer, or localized prostate cancer with
             a current PSA of < 1.0mg/dL on 2 successive evaluations, at least 3 months apart, with
             the most recent evaluation no more than 4 weeks prior to the start of study drug.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS) as measured by documented progression or death from any cause.
Time Frame:Up to 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Over all survival as measured by follow up
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:Number of adverse events
Time Frame:From the first dose of study drug through 30 days after the last dose of study drug
Safety Issue:
Description:All grade 2-5 Adverse events must be recorded on the case report form (CRF)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Duke University

Trial Keywords

  • pembrolizumab
  • XELOX
  • gastric cancer

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