Pembrolizumab, Capecitabine, and Radiation Therapy in Treating Patients With Mismatch-Repair Deficient and Epstein-Barr Virus Positive Gastric Cancer

NCT03257163 | Active Not Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: Pro20170000375NCI-2017-01429071702P30CA072720
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 4

Brief Summary

This phase II trial studies how well pembrolizumab works with capecitabine and radiation therapy in treating patients with mismatch repair deficient and Epstein-Barr virus positive gastric cancer. Monoclonal antibodies, such as pembrolizumab may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving pembrolizumab, capecitabine and radiation therapy may work better at treating gastric cancer.

Conditions

Stage IB Gastric Cancer AJCC v7; Stage IIA Gastric Cancer AJCC v7; Stage IIB Gastric Cancer AJCC v7; Stage III Gastric Cancer AJCC v7; Epstein-Barr Virus Positive; Gastric Adenocarcinoma; Mismatch Repair Protein Deficiency; Stage II Gastric Cancer AJCC v7; Stage IIIA Gastric Cancer AJCC v7; Stage IIIB Gastric Cancer AJCC v7; Stage IIIC Gastric Cancer AJCC v7

Outcome Measures

Primary Outcomes (1)

• Recurrence-free survival (RFS) rate

  At the time of analysis (after 18 months of accrual and 18 additional months of follow-up), will compute a Kaplan-Meier survival curve and will compare the observed survival rate at three years to the historical level of 0.45.

  3 years

Study Arms (1)

Treatment (pembrolizumab, capecitabine, radiation therapy)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks, patients undergo surgery. Beginning up to 56 days after surgery, patients receive pembrolizumab IV over 30 minutes on day 1 and capecitabine PO BID on days 1-14. Treatment repeats every 21 days for up to 5 courses in the absence of disease progression or unacceptable toxicity. Within 2-6 weeks of resting, patients continue to receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 11 courses in the absence of disease progression or unacceptable toxicity. Beginning course 4, patients undergo radiation therapy over 15-30 minutes on days 1-5 for up to 5 weeks.

Drug: Capecitabine; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Radiation: Radiation Therapy

Interventions

Capecitabine DRUG

Given PO

Treatment (pembrolizumab, capecitabine, radiation therapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab, capecitabine, radiation therapy)

Pembrolizumab BIOLOGICAL

Given IV

Treatment (pembrolizumab, capecitabine, radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Treatment (pembrolizumab, capecitabine, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent for the trial
• Must have operable gastric adenocarcinoma, T2-T4a, N0-N3, M0
• Staging evaluation within 42 days of enrollment consisting of staging laparoscopy, computed tomography (CT) scan of the abdomen and pelvis, and positron emission tomography (PET) scan will be acquired; also endoscopic ultrasound (EUS) tumor and nodal staging will be required
• Mismatch repair deficiency as identified by immunohistochemistry or other institutional standard, or Epstein-Barr virus positivity as determined by in situ hybridization or other institutional standard
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained up to 10 weeks (70 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen (if available from prior biopsy) only upon agreement from the sponsor
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) \>= 1,500 /mcL
• Platelets \>= 100,000 / mcL
• Hemoglobin \>= 7 g/dL or \>= 5.6 mmol/L with transfusion or erythropoietin (EPO) dependency
• Serum creatinine =\< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate \[GFR\] can also be used in place of creatinine or creatinine clearance \[CrCl\]) \>= 60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN
• Serum total bilirubin =\< 1.5 X ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X ULN
• Albumin \>= 2.5 mg/dL
• International normalized ratio (INR) or prothrombin time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (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

You may not qualify if:

• Presence of metastatic disease is not allowed; subjects must be evaluated with imaging consisting of CT scan and PET scan prior to enrollment for protocol therapy to exclude metastatic disease
• Prior chemotherapy, adjuvant therapy, or radiotherapy for gastric cancer
• Prior radiotherapy that overlaps with planned radiotherapy portal
• 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 a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
• 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: subjects with =\< grade 2 neuropathy are an exception to this criterion and may qualify for the study
• 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 a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Evidence of interstitial lung disease
• Has an active infection requiring systemic therapy

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Emory University

Atlanta, Georgia, 30308, United States

Location

RWJBarnabas Health - Robert Wood Johnson University Hospital, Hamilton

Hamilton, New Jersey, 08690, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Capecitabine; pembrolizumab; Radiotherapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Therapeutics

Study Officials

• Salma Jabbour

  Rutgers Cancer Institute of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Department of Radiation Oncology

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 22, 2017
• Study Start: September 29, 2017
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)