Perioperative Treatment in Resectable Gastric Cancer With Spartalizumab (PDR001) in Combination With Fluorouracil, Leucovorin, Oxaliplatin, and Docetaxel (FLOT): A Phase II Study (GASPAR)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 67
- 试验地点
- 14
- 主要终点
- Pathologic response after pre-operative treatment
研究概览
简要总结
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
FLOT regimen plus Spartalizumab
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)
干预措施: perioperative treatment (Drug)
结局指标
主要结局
Pathologic response after pre-operative treatment
时间窗: 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
Pathologic Response After Pre-operative Treatment
时间窗: 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).
次要结局
- Evaluate the impact of perioperative treatment on disease-free survival(Through study completion, an average of 5 follow-up year)
- Evaluate the impact of perioperative treatment on overall survival(Up to death)
- The correlation between pathologic Complete response and survival outcomes (disease-free and overall survival)(At surgery, an average 3 months after treatment initiation)
- Treatment-Related Adverse Events(Toxicities occurring up to 1 month after the end of treatment)
- Evaluate the Impact of Perioperative Treatment on Disease-free Survival(24 months after study enrollment)
- Evaluate the Impact of Perioperative Treatment on Overall Survival(24 months after enrollment)
- The Correlation Between Pathologic Complete Response and Survival Outcomes (Disease-free and Overall Survival)(At surgery, an average 3 months after treatment initiation)