GASPAR: Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT)
Study Details
Study Description
Brief Summary
Multicenter, open-label, non randomized, phase 2 trial in resectable gastric or gastroesophageal junction adenocarcinoma: Perioperative Treatment by Spartalizumab (PDR001) in Combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT)
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: FLOT regimen plus Spartalizumab Standard FLOT regimen Docetaxel 50 mg/m² IV infusion on D1 Oxaliplatine 85 mg/m² IV infusion on D1 Leucovorin 200 mg/m² IV infusion on D1 Fluorouracile 2600 mg/m² 24 h IV infusion on D1 with Spartalizumab PDR001 Patients will received the fixed dose of 400 mg per IV infusion on D1 every four weeks (q4w) for 2 pre-operative cycles (8 weeks) and 2 post-operative cycles (8 weeks) |
Drug: perioperative treatment
FLOT + Spartalizumab
|
Outcome Measures
Primary Outcome Measures
- Pathologic response after pre-operative treatment [At surgery, an average 3 months after treatment initiation]
Proportion of patients with pCR (pathologic complete response) in the primary tumour defined as: no tumour residue found in the tissue collected during the surgery evaluated by the pathologist
Secondary Outcome Measures
- Evaluate the impact of perioperative treatment on disease-free survival [Through study completion, an average of 5 follow-up year]
Disease-free survival (DFS) defined as time between inclusion and first disease progression
- Evaluate the impact of perioperative treatment on overall survival [Up to death]
Overall survival (OS) defined as the time between inclusion and death whatever cause;
- The correlation between pathologic Complete response and survival outcomes (disease-free and overall survival) [At surgery, an average 3 months after treatment initiation]
Proportion of patients with margin-free resection (R0), defined as a microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed
- Treatment-Related Adverse Events [Toxicities occurring up to 1 month after the end of treatment]
Type, grade and number of Adverse Events as Assessed by CTCAE v5.0
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 18 years
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Untreated localized gastric or GEJ adenocarcinoma considered resectable (clinical stage ≥cT2 and/or cN+ and no metastasis)
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Histologically confirmed adenocarcinoma
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ECOG performance status score of 0 or 1
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Tumor tissue must be provided for biomarker analyses (fresh or archival with an FFPE tissue block)
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All subjects must consent to allow the acquisition of blood samples for performance of correlative studies
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Screening laboratory values must meet the following criteria:
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WBC ≥ 2000/ mm³
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Neutrophils ≥ 1500/ mm³
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Platelets ≥ 100 000/ mm³
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Hemoglobin ≥ 9.0 g/dL
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Bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 3 x ULN
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Measured or calculated creatinine ≥ 50 ml/min clearance (CrCl) (using the Cockcroft-Gault formula)
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Potassium ≥ LLN
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Magnesium ≥ LLN
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Calcium ≥ LLN
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Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72h before study start
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Subject in reproductive age must be willing to use adequate contraception during the study and at least 9 months in men and 12 months in women after the last dose of investigational drug. In addition, given the toxicities observed on the male reproductive system, a conservation of gametes will be proposed for men, as usually in routine practice
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Subject affiliated to a social security regimen
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Patient has signed informed consents obtained before any trial related activities and according to local guidelines
Exclusion Criteria:
Subject with any distant metastasis
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Subject with no recovering from the effects of major surgery or significant traumatic injury within 14 days before inclusion
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Documented significant cardiovascular disease within the past 6 months before the first dose of study treatment, including: history of congestive heart failure (defined as NYHA III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis
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History of anterior organ transplant, including stem cell allograft
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Pneumonitis or interstitial lung disease
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History of other malignancy within the previous 3 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma)
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Subject with active, known, or suspected autoimmune disease
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Subject with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment GASPAR Protocol - EUDRACT number: 2020-004497-21 - version 1.3 / 2021-01-18 Page 8 sur 44
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Known history of HIV or HBV infection
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Known active HCV infection
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Known history of active tuberculosis
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Vaccination with live vaccine within 30 days before the first dose of study treatment
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Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
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Recent or concomitant treatment with brivudine (herpes virostatic)
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Prior anticancer therapy for the current malignancy
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Known hypersensitivity to any of the study drugs or their excipients
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Chronic inflammable gastro-intestinal disease
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Uracilemia ≥ 16 ng/ml
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QT/QTc > 450 msec for men and > 470 msec for women
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Peripheral neuropathy ≥ Grade II
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Uncontrolled diabetes
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Active infection requiring systemic therapy
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Participation in another therapeutic clinical study
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Patient deprived of liberty or placed under the authority of a tutor
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Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Centre François Baclesse | Caen | France |
Sponsors and Collaborators
- Centre Francois Baclesse
- National Cancer Institute, France
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2020-004497-21