Perioperative Treatment in Resectable Gastric Cancer with Spartalizumab (PDR001) in Combination with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT): A phase II study (GASPAR)

Phase 2

Not yet recruiting

• Conditions: Resectable Gastric Cancer

• Registration Number: 2024-516299-13-00
• Lead Sponsor: Centre Francois Baclesse

Brief Summary

To evaluate the pathologic response after pre-operative treatment

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-09-05
• Last Update Posted: 2024-09-05

Recruitment & Eligibility

• Status: Authorised, recruitment pending
• Sex: Not specified
• Target Recruitment: 68

Inclusion Criteria

• Age ≥ 18 years

• Subject affiliated to a social security regimen

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

• 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: o WBC ≥ 2000/ mm³ o Neutrophils ≥ 1500/ mm³ o Platelets ≥ 100 000/ mm³ o Hemoglobin ≥ 9.0 g/dL o Bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 3 x ULN o Measured or calculated creatinine ≥ 50 ml/min clearance (CrCl) (using the Cockcroft-Gault formula) o Potassium ≥ LLN o Magnesium ≥ LLN o 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

Exclusion Criteria

• Subject with any distant metastasis

• 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

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

• 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

• 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

• Known history of HIV or HBV infection

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary endpoint is the proportion of patients with pCR in the primary tumour defined as: no tumour residue found in the tissue collected during the surgery evaluated by the pathologist		The primary endpoint is the proportion of patients with pCR in the primary tumour defined as: no tumour residue found in the tissue collected during the surgery evaluated by the pathologist

Secondary Outcome Measures

Name	Time	Method
- Disease-free survival (DFS) defined as time between inclusion and first progression according to RECIST v1.1 criteria or death whatever cause (in the absence of progression); patients without disease progression or death at the time of analysis will be censored at the time of the latest date of assessment		- Disease-free survival (DFS) defined as time between inclusion and first progression according to RECIST v1.1 criteria or death whatever cause (in the absence of progression); patients without disease progression or death at the time of analysis will be censored at the time of the latest date of assessment
- Overall survival (OS) defined as the time between inclusion and death whatever cause; any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive		- Overall survival (OS) defined as the time between inclusion and death whatever cause; any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive
- 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		- 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
- Correlation between pCR and DFS		- Correlation between pCR and DFS
- Correlation between pCR and OS		- Correlation between pCR and OS
- Toxicities of the combination Spartalizumab + FLOT regimen according to NCI CTCAE criteria v5.0		- Toxicities of the combination Spartalizumab + FLOT regimen according to NCI CTCAE criteria v5.0
- Post-operative morbidity, defined post-operative complications grades II-V according to Clavien-Dindo classification during surgery, within 30 days after surgery or during the hospital stay		- Post-operative morbidity, defined post-operative complications grades II-V according to Clavien-Dindo classification during surgery, within 30 days after surgery or during the hospital stay
- Post-operative mortality, defined as the rate of patients died due to any cause during the 30 days post-surgery		- Post-operative mortality, defined as the rate of patients died due to any cause during the 30 days post-surgery

Trial Locations

Locations (15)

Institut De Cancerologie De L Ouest; 🇫🇷 Saint-Herblain Cedex, France

Centre Hospitalier Universitaire De Poitiers; 🇫🇷 Poitiers, France

Centre Hospitalier Universitaire Reims; 🇫🇷 Reims Cedex, France

Centre Francois Baclesse; 🇫🇷 Caen Cedex 5, France

Hopital Saint Louis; 🇫🇷 Paris, France

Institut Regional Du Cancer De Montpellier; 🇫🇷 Montpellier Cedex 5, France

Centre Hospitalier Universitaire De Toulouse; 🇫🇷 Toulouse, France

Institut Bergonie; 🇫🇷 Bordeaux, France

Centre Hospitalier Regional De Marseille; 🇫🇷 Marseille, France

Institut Mutualiste Montsouris; 🇫🇷 Paris, France

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Institut De Cancerologie De L Ouest

🇫🇷Saint-Herblain Cedex, France

Sandrine Hiret

Site contact

0240679978

Sandrine.Hiret@ico.unicancer.fr