Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT)

• Status: Recruiting
• Trial end date: 2027-03-01
• Target enrollment: 0
• Participant gender: All

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)

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Centre Francois Baclesse
• Collaborator: National Cancer Institute, France

Criteria

Inclusion Criteria:

• Age ≥ 18 years

• Untreated localized gastric or GEJ adenocarcinoma considered resectable (clinical stage ≥cT2 and/or cN+ and no metastasis)

• Histologically confirmed adenocarcinoma

• ECOG performance status score of 0 or 1

• Tumor tissue must be provided for biomarker analyses (fresh or archival with an FFPE tissue block)

• All subjects must consent to allow the acquisition of blood samples for performance of correlative studies

• Screening laboratory values must meet the following criteria:

• WBC ≥ 2000/ mm³

• Neutrophils ≥ 1500/ mm³

• Platelets ≥ 100 000/ mm³

• Hemoglobin ≥ 9.0 g/dL

• Bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 3 x ULN

• Measured or calculated creatinine ≥ 50 ml/min clearance (CrCl) (using the Cockcroft-Gault formula)

• Potassium ≥ LLN

• Magnesium ≥ LLN

• Calcium ≥ LLN

• Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72h before study start

• 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

• Subject affiliated to a social security regimen

• Patient has signed informed consents obtained before any trial related activities and according to local guidelines

Exclusion Criteria:

Subject with any distant metastasis

• Subject with no recovering from the effects of major surgery or significant traumatic injury within 14 days before inclusion

• 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

• History of anterior organ transplant, including stem cell allograft

• Pneumonitis or interstitial lung disease

• History of other malignancy within the previous 3 years (except for appropriately treated in-situ cervix carcinoma and non-melanoma skin carcinoma)

• Subject with active, known, or suspected autoimmune disease

• 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

• Known history of HIV or HBV infection

• Known active HCV infection

• Known history of active tuberculosis

• Vaccination with live vaccine within 30 days before the first dose of study treatment

• 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

• Recent or concomitant treatment with brivudine (herpes virostatic)

• Prior anticancer therapy for the current malignancy

• Known hypersensitivity to any of the study drugs or their excipients

• Chronic inflammable gastro-intestinal disease

• Uracilemia ≥ 16 ng/ml

• QT/QTc > 450 msec for men and > 470 msec for women

• Peripheral neuropathy ≥ Grade II

• Uncontrolled diabetes

• Active infection requiring systemic therapy

• Participation in another therapeutic clinical study

• Patient deprived of liberty or placed under the authority of a tutor

• Patient assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol