KeyLargo: Pembrolizumab + Oxaliplatin + Capecitabine in Gastric Cancer

Sponsor

Duke University (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03342937

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Locations

Arm

60.9

Anticipated Duration (Months)

5.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will be conducted in two stages: 1) safety validation and 2) dose expansion

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.
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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer Esophagus Cancer	Drug: Oxaliplatin+Capecitabine+Pembrolizumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Single Arm, Phase II Study of Pembrolizumab, Oxaliplatin, and Capecitabine in the First Line Treatment of Patients With Gastro-esophageal Cancer.

Actual Study Start Date :

Jan 11, 2018

Anticipated Primary Completion Date :

Feb 7, 2023

Anticipated Study Completion Date :

Feb 7, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oxaliplatin+Capecitabine+Pembrolizumab	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: Safety validation part: all Cycles are 21 days in length. Dose Expansion part: Cycle 1 is 28 days in length. Cycle 2 and beyond are 21 days.

Arm

Intervention/Treatment

Experimental: Oxaliplatin+Capecitabine+Pembrolizumab

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: Safety validation part: all Cycles are 21 days in length. Dose Expansion part: Cycle 1 is 28 days in length. Cycle 2 and beyond are 21 days.

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) as measured by documented progression or death from any cause. [Up to 3 years]

Secondary Outcome Measures

Over all survival as measured by follow up [Up to 3 years]
Number of adverse events [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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Absolute neutrophil count (ANC) ≥ 1500 µl
Platelets ≥ 100,000/µl
Hemoglobin (Hgb) ≥ 9 g/dL
Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
AST/ALT ≤ 2 x ULN without liver metastasis; ≤ 5 x ULN with liver metastasis
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johnston Health Services Corporation	Clayton	North Carolina	United States	27520
2	Duke Cancer Center, Duke University	Durham	North Carolina	United States	27710
3	Maria Parham Healthcare Association	Henderson	North Carolina	United States	27536
4	Scotland Health Care System	Laurinburg	North Carolina	United States	28352
5	Southeastern Regional Medical Center	Lumberton	North Carolina	United States	28358
6	Johnston Health Services Corporation	Smithfield	North Carolina	United States	27577
7	Lexington Medical Center	West Columbia	South Carolina	United States	29169