Pembrolizumab, Capecitabine, and Radiation Therapy in Treating Patients with Mismatch-Repair Deficient and Epstein-Barr Virus Positive Gastric Cancer
18 Years and older, Male and Female
071702 (primary)
NCI-2017-01429
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.
Objectives
PRIMARY OBJECTIVES:
I. To assess efficacy (disease-free survival) of operable gastric cancer treated with PD-1 blockade using pembrolizumab.
SECONDARY OBJECTIVES:
I. To characterize the safety and tolerability of pembrolizumab in the preoperative setting and postoperative setting with chemoradiation.
II. To evaluate response rates, recurrence rates, and patterns of recurrence/metastasis.
III. To characterize adverse events (AE) of pembrolizumab in combination with radiation therapy and capecitabine.
IV. To evaluate overall survival rates.
TERTIARY OBJECTIVES:
I. To assess T cell responses and pathological responses in the tumor specimen.
II. To correlate PD-L1 expression in tumor tissue and stroma with tumor tissue response.
III. To evaluate ribonucleic acid (RNA) expression via Nanostring technology with tumor tissue response.
OUTLINE:
Patients receive pembrolizumab intravenously (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 orally (PO) twice daily (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.
After completion of study treatment, patients are followed up every 12 weeks for 1 year, every 16 weeks for 2 years, every 4 months for year 2, and every 6 months for 2 years.
Eligibility
- 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
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 7 days of enrollment; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication; Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
- Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy; Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
Treatment Sites in Georgia
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