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KeyLargo: Pembrolizumab + Oxaliplatin + Capecitabine in Gastric Cancer

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ClinicalTrials.gov Identifier: NCT03342937
Recruitment Status : Recruiting
First Posted : November 17, 2017
Last Update Posted : March 29, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE November 10, 2017
First Posted Date  ICMJE November 17, 2017
Last Update Posted Date March 29, 2019
Actual Study Start Date  ICMJE January 11, 2018
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 10, 2017)
Progression-free survival (PFS) as measured by documented progression or death from any cause. [ Time Frame: Up to 2 years ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03342937 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 28, 2017)
  • Over all survival as measured by follow up [ Time Frame: Up to 2 years ]
  • Number of adverse events [ Time Frame: From the first dose of study drug through 30 days after the last dose of study drug ]
    All grade 2-5 Adverse events must be recorded on the case report form (CRF)
Original Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2017)
  • Over all survival as measured by follow up [ Time Frame: Up to 2 years ]
  • Number of adverse events [ Time Frame: From the first dose of study drug through 30 days after the last dose of study drug ]
    All grade 2-5 Adverse events must be recorded on the CRF
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE KeyLargo: Pembrolizumab + Oxaliplatin + Capecitabine in Gastric Cancer
Official Title  ICMJE A Single Arm, Phase II Study of Pembrolizumab, Oxaliplatin, and Capecitabine in the First Line Treatment of Patients With Gastro-esophageal Cancer.
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Gastric Cancer
  • Esophagus Cancer
Intervention  ICMJE Drug: Oxaliplatin+Capecitabine+Pembrolizumab

For each cycle: Oxaliplatin 130 mg/m2 IV on Day1, Capecitabine 825 or 1000 mg/m2 PO, BID Days on Days1-14, Pembrolizumab 200 mg IV on Day 1.

This study has 2 parts:

  1. Safety validation part: all Cycles are 21 days in length.
  2. Dose Expansion part: Cycle 1 is 28 days in length. Cycle 2 and beyond are 21 days.
Study Arms  ICMJE Experimental: Oxaliplatin+Capecitabine+Pembrolizumab
Intervention: Drug: Oxaliplatin+Capecitabine+Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 10, 2017)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Taylor Kennedy Frenchi 919-668-1861 taylor.kennedy.frenchi@duke.edu
Contact: Ireka Burrus, MSW 919-668-1861 ireka.burrus@duke.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03342937
Other Study ID Numbers  ICMJE Pro00080566
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Duke University
Study Sponsor  ICMJE Duke University
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Hope Uronis, MD Duke University
PRS Account Duke University
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP