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

Resectable Carcinoma Clinical Trial

— GASPAR  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04736485
• Other study ID #: 2020-004497-21
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 28, 2021
• Est. completion date: March 2027

Study information

• Verified date: December 2022
• Source: Centre Francois Baclesse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 67
• Est. completion date: March 2027
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Gastric Cancer by AJCC V8 Stage
• Resectable Carcinoma
• Stomach Neoplasms

Intervention

Drug:
• perioperative treatment
FLOT + Spartalizumab

Locations

Country	Name	City	State
France	CHU Besançon	Besançon
France	Centre François Baclesse	Caen
France	Centre Georges Francois Leclerc	Dijon
France	Chru Lille	Lille
France	APHM Marseille	Marseille
France	Institut Régional Cancer	Montpellier
France	APHP St Louis	Paris
France	Institut Mutualiste Montsouris	Paris
France	CHU Poitiers	Poitiers
France	CHU Robert Debré	Reims
France	Centre Eugène Marquis	Rennes
France	ICO St Herblain	Saint-Herblain
France	CH St Malo	Saint-Malo

Sponsors (2)

Lead Sponsor	Collaborator
Centre Francois Baclesse	National Cancer Institute, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathologic response after pre-operative treatment	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	At surgery, an average 3 months after treatment initiation
Secondary	Evaluate the impact of perioperative treatment on disease-free survival	Disease-free survival (DFS) defined as time between inclusion and first disease progression	Through study completion, an average of 5 follow-up year
Secondary	Evaluate the impact of perioperative treatment on overall survival	Overall survival (OS) defined as the time between inclusion and death whatever cause;	Up to death
Secondary	The correlation between pathologic Complete response and survival outcomes (disease-free and overall survival)	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	At surgery, an average 3 months after treatment initiation
Secondary	Treatment-Related Adverse Events	Type, grade and number of Adverse Events as Assessed by CTCAE v5.0	Toxicities occurring up to 1 month after the end of treatment