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

Centre Francois Baclesse

Status and phase: Active, not recruiting; Phase 2

Conditions: Gastric Cancer by AJCC V8 Stage; Resectable Carcinoma

Treatments: Drug: perioperative treatment

Study type: Interventional

Funder types: Other

Identifiers

NCT04736485

2020-004497-21

Details and patient eligibility

About

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)

Enrollment: 67 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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67 participants in 1 patient group

FLOT regimen plus Spartalizumab

Experimental group

Description:

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)

Treatment:

Drug: perioperative treatment