Clinical trial NCT04736485: Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT)
Official title: Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT): A Phase II Study (GASPAR)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer by AJCC V8 Stage
Resectable Carcinoma
Keywords: perioperative
spartalizumab
PDR001
Gastric Cancer
Lead sponsor: Centre Francois Baclesse
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
First posted: 2021-02-03
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility 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

Primary outcomes:
measure: Pathologic response after pre-operative treatment
timeFrame: At surgery, an average 3 months after treatment initiation
Secondary outcomes:
measure: Evaluate the impact of perioperative treatment on disease-free survival
timeFrame: Through study completion, an average of 5 follow-up year
measure: Evaluate the impact of perioperative treatment on overall survival
timeFrame: Up to death
measure: The correlation between pathologic Complete response and survival outcomes (disease-free and overall survival)
timeFrame: At surgery, an average 3 months after treatment initiation
measure: Treatment-Related Adverse Events
timeFrame: Toxicities occurring up to 1 month after the end of treatment
Other outcomes:
Locations:
city: Besançon
country: France
facility: CHU Besançon
city: Caen
country: France
facility: Centre François Baclesse
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Lille
country: France
facility: Chru Lille
city: Marseille
country: France
facility: APHM Marseille
city: Montpellier
country: France
facility: Institut Régional Cancer
city: Paris
country: France
facility: APHP St Louis
city: Paris
country: France
facility: Institut Mutualiste Montsouris
city: Poitiers
country: France
facility: CHU Poitiers
city: Reims
country: France
facility: CHU Robert Debré
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Saint-Herblain
country: France
facility: ICO St Herblain
city: Saint-Malo
country: France
facility: CH St Malo
Study officials:
References:
citation: Dos Santos M, Lequesne J, Leconte A, Corbinais S, Parzy A, Guilloit JM, Varatharajah S, Brachet PE, Dorbeau M, Vaur D, Weiswald LB, Poulain L, Le Gallic C, Castera-Tellier M, Galais MP, Clarisse B. Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR). BMC Cancer. 2022 May 12;22(1):537. doi: 10.1186/s12885-022-09623-z.