A Phase II Study of Chemotherapy and Immune Checkpoint Blockade With Pembrolizumab in the Perioperative and Maintenance Treatment of Locoregional Gastric or GE Junction Adenocarcinoma.
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Gastric Cancer
- Sponsor
- Gulam Manji
- Enrollment
- 49
- Locations
- 4
- Primary Endpoint
- Pathologic Complete Response (pCR) Rate
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a non-randomized, multi-site, open-label trial of pembrolizumab and chemotherapy in subjects with gastric or gastroesophageal (GE) junction adenocarcinoma. The purpose of this study is to determine and evaluate the efficacy of combination therapy with immune checkpoint blockade and chemotherapy used in the perioperative period in eradicating micrometastatic disease; and to compare paired tissue and serum samples (pre-treatment and post-treatment) from individually treated patients to explore the immune effects of combination therapy and predictors of response.
Detailed Description
Gastric cancer is one of the most common cancers worldwide. Surgical resection is the primary treatment for gastric cancer but most patients present with locally advanced disease and recurrence is common after surgery. Many patients (35%) will have early recurrence within 6-9 months of surgery indicating the need for more aggressive upfront therapy in these subjects. In addition, the majority of patients will ultimately have recurrence and 5 year survival rates are 35-40% despite aggressive therapy. The ability to combine immunotherapy with pembrolizumab gives the potential to increase therapeutic options while continuing standard of care chemotherapy. The particular use of maintenance therapy may delay or eliminate the growth of residual micrometastatic disease and lead to durable disease control. Additionally, this study provides the foundation for substantial correlative work to define tumor and patient characteristics that may predict for response to pembrolizumab in gastric cancer. The initial primary outcome of Disease Free Survival (DFS) was changed to pathologic complete response rate (pCR) on November 24, 2020, at which time no formal data analysis had been preformed.
Investigators
Gulam Manji
Professor of Medicine
Columbia University
Eligibility Criteria
Inclusion Criteria
- •Have previously untreated localized gastric or GE junction adenocarcinoma as defined by T2 or greater primary lesion or the presence of any positive nodes- N+(clinical nodes) without evidence of metastatic disease.
- •Plan to proceed to surgery following peri-operative chemotherapy based on standard staging studies per local practice.
- •Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
- •Be at least 18 years of age on day of signing informed consent.
- •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 6 weeks (42 days) prior to initiation of treatment on Day
- •Have a performance status of 0 or 1 on the ECOG Performance Scale.
- •Demonstrate adequate organ function as defined below, all screening labs should be performed within 14 days of treatment initiation.
- •Adequate Organ Function Laboratory Values
- •Absolute neutrophil count (ANC) ≥1,500 /mcL
- •Platelets ≥100,000 / mcL
Exclusion Criteria
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- •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. The use of physiologic doses of corticosteroids (prednisone 10 mf or equivalent) may be approved after consultation.
- •Has a known history of active TB (Bacillus Tuberculosis)
- •Hypersensitivity to pembrolizumab or any of its excipients.
- •Has had any prior chemotherapy, targeted small molecule therapy, or radiation therapy for their current diagnosis.
- •Has a known additional malignancy that is progressing or requires active treatment within 3 years from registration. 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. Subjects with a history of prior malignancy diagnosed and treated greater than 3 years form registration may be considered with consultation of the primary investigator.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •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 known history of prior pneumonitis requiring treatment with steroids, or any evidence of active, non-infectious pneumonitis.
- •Has an active infection requiring systemic therapy which is not expected to have resolved by Cycle 1 Day 1 dosing.
Arms & Interventions
Pembrolizumab
All study subjects will receive standard of care chemotherapy regimen for 3 cycles prior to and 3 cycles following surgery in combination with Pembrolizumab with an additional cycle of Pembrolizumab (4 total) in the pre-operative period. Additionally subjects will complete 12 months of maintenance Pembrolizumab (14 additional doses to complete 17 post-operative cycles) following completion of post-operative chemotherapy. Standard of care combination chemotherapy regimen has a 21-day cycle.
Intervention: Pembrolizumab
Pembrolizumab
All study subjects will receive standard of care chemotherapy regimen for 3 cycles prior to and 3 cycles following surgery in combination with Pembrolizumab with an additional cycle of Pembrolizumab (4 total) in the pre-operative period. Additionally subjects will complete 12 months of maintenance Pembrolizumab (14 additional doses to complete 17 post-operative cycles) following completion of post-operative chemotherapy. Standard of care combination chemotherapy regimen has a 21-day cycle.
Intervention: Standard of care chemotherapy regimen
Outcomes
Primary Outcomes
Pathologic Complete Response (pCR) Rate
Time Frame: Up to 34 months
Number of subjects with absence of viable tumor on surgical resection specimen as determined by local pathology review.
Secondary Outcomes
- Overall Survival (OS)(Treatment initiation until death or study end, whichever occurs first (up to approximately 5 years))
- Disease Free Survival (DFS)(Treatment initiation to progression, recurrence, death or study end, whichever comes first (up to approximately 5 years))
- Overall Response Rate (ORR)(Up to 34 months)