Gastric or Gastroesophageal Junction Adenocarcinoma MedDRA version: 21.0 Level: LLT Classification code 10056267 Term: Gastroesophageal cancer System Organ Class: 100000004864
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have previously untreated localized gastric or GEJ adenocarcinoma as defined by T3 or greater primary lesion or the presence of any positive nodes- N+(clinical nodes) without evidence of metastatic disease. Siewert type 2 or 3 tumors are eligible. Enrollment of participants with Siewert type 1 tumors will be limited to those for whom the planned treatment is perioperative chemotherapy and resection. Tumor staging prior to enrollment must consist of at least 1 imaging modality: computed tomography (CT) or magnetic resonance imaging (MRI). 2.Be at least 18 years of age on the day of signing informed consent 3.Have an ECOG performance status of 0 to 1, to be performed within 3 days prior to the first dose of study treatment 4.Have a life expectancy of greater than 6 months 5.Male participants of childbearing potential must agree to use an adequate method of contraception as outlined in Appendix 3, for the course of the study through 180 days after the last dose of chemotherapy. 6.Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 7.Female participants of childbearing potential must be willing to use an adequate method of contraception as outlined in Appendix 3, for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after teh last dose of pembrolizumab, whichever is greater. 8.The participant provides written informed consent for the study. The participant may also provide consent for Future Biomedical Research. However, the participant may participate in the main study without participating in Future Biomedical Research. 9.Plan to proceed to surgery following pre operative chemotherapy based on standard staging studies per local practice. 10.Be willing to provide tissue from a tumor lesion at baseline and at time of surgery 11.Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of study treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 500 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 500
Exclusion criteria
Exclusion criteria: 1.Has a history of (non infectious) pneumonitis that required steroids or has current pneumonitis. 2.Has an active infection requiring systemic therapy 3.Has a diagnosis of immunodeficiency 4.Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. 5.Has a known severe hypersensitivity (= Grade 3) to pembrolizumab, its active substance and/or any of its excipients. (Refer to the respective IB for a list of excipients.) 6.Has a known severe hypersensitivity (= Grade 3) to any of the study chemotherapy agents and/or to any of their excipients. 7.Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, 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) is not considered a form of systemic treatment and is allowed. 8.Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority. 9.Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. 10.Has a known history of active tuberculosis (TB; Bacillus tuberculosis). 11. Female participants: Is pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater. Male participants: Is expecting to father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy. 12.Has a history or current evidence of any condition (eg. known deficiency of the enzyme dihydropyrimidine dehydrogenase [DPD]), therapy or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 13. Has had an allogeneic tissue/solid organ transplant. 14. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study. 15.A woman of child-bearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to receiving first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 16.Has received prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (ie, CTLA-4, OX-40, CD137) or has previously participated in a Merck pembrolizumab (MK 3475) clinical study. 17.Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy. 18.Is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main Study (XP/FP): 1. To evaluate event-free survival (EFS) 2. To evaluate the rate of pathological complete response based on central review. 3. To evaluate overall survival (OS) FLOT Cohort: 4. To evaluate the safety and tolerability of pembrolizumab in combination with docetaxel, oxaliplatin, 5-FU, and leucovorin (calcium folinate) (FLOT);Secondary Objective: Main Study (XP/FP), and Main Study (XP/FP) and FLOT Cohort combined: 1. To evaluate the safety and tolerability of pembrolizumab in combination with chemotherapy Main Study (XP/FP): 2. To evaluate the disease-free survival (DFS) as assessed by investigator for participants who are disease free after surgery Main Study (XP/FP) and FLOT Cohort combined: 3. To evaluate OS 4. To evaluate EFS;Primary end point(s): Main study (XP/FP): - Event-free Survival (EFS) assessed by investigators - Rate of Pathological Complete Response (pathCR) - Overall Survival (OS) FLOT Cohort: - AEs; Study treatment discontinuations due to AEs;Timepoint(s) of evaluation of this end point: IA1: ~41 months after first participant randomized. Primary purpose: final pathCR rate analysis, interim EFS analysis and OS analyses. IA2: ~7 months after IA1. Primary purpose: interim EFS analysis and OS analyses IA3: ~12 months after IA2. Primary purpose: final EFS analysis and interim OS analysis. Final analysis (FA): ~12 months after IA3. Primary purpose: final OS analysis. Safety: Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Main study (XP/FP): - Disease free Survival (DFS) assessed by investigators - AEs; Study treatment discontinuations due to AEs Main study (XP/FP) and FLOT Cohort Combined: - Overall Survival (OS) - Event free Survival (EFS) assessed by investigators - AEs; Study treatment discontinuations due to AEs;Timepoint(s) of evaluation of this end point: IA1: ~ 41 months after first participant randomized. Primary purpose: interim EFS and OS analyses. IA2: ~ 7 months after IA1. Primary purpose: interim EFS and OS analyses IA3:~ 12 months after IA2. Primary purpose: final EFS analysis and interim OS analysis. Final analysis (FA):~ 12 months after IA3. Primary purpose: final OS analysis. DFS: Up to approximately 2 years Safety: Throughout the study | — |
Countries
Belgium, Brazil, Canada, Chile, Estonia, France, Germany, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Poland, Russian Federation, Singapore, Taiwan, United Kingdom, United States
Contacts
Public ContactChie-Schin Shih
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Outcome results
None listed