Gastric Cancer by AJCC V8 Stage, Resectable Carcinoma
Conditions
Keywords
perioperative, spartalizumab, PDR001, Gastric Cancer
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)
Interventions
FLOT + Spartalizumab
Sponsors
Centre Francois Baclesse
National Cancer Institute, France
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Response After Pre-operative Treatment | At surgery, an average 3 months after treatment initiation | 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. For the primary objective, the pathologic response after pre-operative treatment will be assessed by the local experienced pathologists. Tumour regression grade will be quantified using the Becker regression criteria, which are based on the estimation of the percentage of vital tumour cells in relation to the macroscopically identifiable tumour bed and include the following categories: * TRG1a (equivalent to pathological complete regression; no residual tumour cells); * TRG1b (subtotal regression; \<10% residual tumour cells); * TRG2 (partial regression; 10-50% residual tumour cells); and * TRG3 (minor or no regression; \>50% residual tumour cells). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Impact of Perioperative Treatment on Disease-free Survival | 24 months after study enrollment | Disease-free survival (DFS) defined as time between inclusion and first disease progression. Disease was assessed locally according to RECIST v1.1 (Response Evaluation Criteria in solid Tumors) criteria. |
| Evaluate the Impact of Perioperative Treatment on Overall Survival | 24 months after enrollment | Overall survival (OS) defined as the time between inclusion and death whatever cause; |
| The Correlation Between Pathologic Complete Response and Survival Outcomes (Disease-free and Overall Survival) | At surgery, an average 3 months after treatment initiation | 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 |
| Treatment-Related Adverse Events | Toxicities occurring up to 1 month after the end of treatment | Type, grade and number of Adverse Events as Assessed by CTCAE v5.0 |
Countries
France
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62 year STANDARD_DEVIATION 11 |
| ECOG 0 : Fully active, able to carry on all pre-disease activities without restriction | 46 Participants |
| ECOG 1 : Restricted in physically strenuous activity but ambulatory and able to carry out light work | 21 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 67 |
| other Total, other adverse events | 67 / 67 |
| serious Total, serious adverse events | 50 / 67 |
Outcome results
None listed