Advanced gastric or gastro-oesophageal junction adenocarcinoma MedDRA version: 20.0 Level: LLT Classification code 10042080 Term: Stomach cancer System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10026476 Term: Malignant neoplasm of stomach System Organ Class: 100000004864
Conditions
Sponsors
Fédération Francophone de Cancérologie Digestive
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age = 18 years. - Body weight > 30kg. - Histologically proven advanced-stage unresectable adenocarcinoma of the stomach or the GEJ (Siewert II or III). - Known MSS/MSI status or tumor tissue available (frozen or paraffin-embedded, primary tumors or metastases) in order to allow determination of MSS/MSI status. The investigator needs to ensure that tumor tissues will be sent after patient randomization. - Failure to platinium-based 1st line therapy or early recurrent disease after surgery with neo-adjuvant and/or adjuvant platinium-based chemotherapy or progression during neo-adjuvant and/or adjuvant platinium-based chemotherapy. - Eligible for a second-line treatment with irinotecan and 5-FU. - Measurable or non-measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). - Eastern Cooperative Oncology Group (ECOG) performance status 0-1. - Adequate organ function: ANC = 1.5 x 109/L, haemoglobin = 9 g/dL, platelets = 100 x 109/L, AST/ALT = 3 x ULN (= 5 x ULN in case of liver metastase(s)), GGT = 3 x ULN (= 5 x ULN in case of liver metastase(s)), bilirubin = 1.5 x ULN, creatinin clearance > 40 mL/min (MDRD). - Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. - Man and woman who childbearing potential agrees to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 6 months after the last treatment intake. - Patient is able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures performed. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 34
Exclusion criteria
Exclusion criteria: - Concurrent enrolment in another clinical study – unless it is an observational study or during the follow-up period of an interventional study. - Receipt of the last dose of anticancer therapy = 2 weeks prior to the first dose of study drug. - Any unresolved significant toxicity NCI CTCAE v4.0 = grade 2 from previous anticancer therapy. - Concurrent use of hormonal therapy for non–cancer-related conditions is acceptable - Major surgical procedure (e.g. exploratory laparoscopy is not considered as a major surgical procedure ) within 28 days prior to the first dose of treatment. - Prior allogeneic bone marrow transplantation or prior solid organ transplantation. - Active or prior documented autoimmune or inflammatory disorders (patients with alopecia, vitiligo, controlled hypo or hyperthyroidism, any chronic skin condition not requiring immunosuppressant therapy are eligible). Patients without active disease in the last 5 years may be included. - Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. - Severe cardiac disorders within 6 months. - Severe liver dysfunction - History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT-scan. - History of leptomeningeal carcinomatosis. Patients whose brain metastases have been treated may participate provided they show radiographic stability In addition, any neurologic symptoms that developed either as a result of the brain metastases or their treatment must have resolved or be stable either, without the use of steroids, or are stable on a steroid dose of =10mg/day of prednisone or its equivalent for at least 14 days prior to the start of treatment - Positive test for HIV, active hepatitis B or hepatitis C, active tuberculosis. - History of active primary immunodeficiency - Current or prior use of immunosuppressive medication within 14 days before the first dose of study drugs (excepted: intranasal, inhaled, topical steroids or local steroid injection –at physiologic dose does not exceed 10 mg/day of prednisone or its equivalent – steroids as premedication for hypersensitivity reactions). - Receipt of live attenuated vaccine within 30 days prior to the first dose of treatment - Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. - Prior treatment with irinotecan, anti-PD1, anti PD-L1, anti-CLTA4 or other immunotherapy for cancer treatment. - Known Uridine Diphosphate Glucuronyltransferase (UGT1A1) or Dihydropyrimidine Dehydrogenase (DPD) enzyme deficiencies. - Active infection requiring intravenous antibiotics at the time of Day 1 of Cycle 1. - Other malignancy within 5 years prior
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Percentage of patients alive and without progression at 4 months of FOLFIRI plus durvalumab versus FOLFIRI plus durvalumab plus tremelimumab in patients with advanced-stage gastric or gastro-oesophageal junction adenocarcinoma and who progressed after a first line chemotherapy (based on RECIST 1.1 rating scale evaluated by the investigator).;Primary end point(s): The primary endpoint is the percentage of patients alive and without radiological progression (according to RECIST 1.1) at 4 months after randomization according to investigator. ;Timepoint(s) of evaluation of this end point: 4 months after the last patient inclusion; Secondary Objective: - Percentage of patients alive and without progression at 4 months according to centralized review - Overall survival (OS) - Time to strategy failure - Safety profile - Quality of life (QoL) - Time to progression (TTP), progression-free survival (median PFS), best objective response rate (BRR) and disease control rate (DCR) according to the investigator and centralized review (according RECIST V1.1 and iRECIST criteria) - Efficacy endpoints (OS, PFS, TTP, BRR and DCR) according to the expression of PD-L1 and others biomarkers (see biological study) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression free survival (PFS) median: Is defined as the time between date of randomization and date of the first radiological progression (according to RECIST 1.1) or death (from any cause), whichever occurs first. Patients alive without progression will be censored at date of last news. Overall Survival (OS): Is defined as the time between date of randomization and date of death (from any cause). Patients alive will be censored at date of last news. Time to progression (TTP): Is defined as the time between date of randomization and the date of first radiological progression (according to RECIST v1.1). Patients without progression will be censored at date of last news or date of death. The death will not be considered as an event. Best Objective Response rate (BRR): Is defined as complete or partial response at the best response evaluation during the treatment according to RECIST v1.1. Disease control rate (DCR) at each timepoint: Is defined as complete or partial response or stable disease at the best response evaluation according to RECIST v1.1. Time to strategy failure: Is defined as the time between randomization date and date of death (from any cause) or the date of first radiological progression in the FOLFIRI + durvalumab arm or date of the second radiological progression after re-introduction of tremelimumab in the FOLFIRI plus durvalumab plus tremelimumab arm or date of definitive discontinuation. In case a treatment is stopped for toxicity reason but re-introduced later for progression, then this progression will not be considered for this endpoint. Safety profile Toxicities will be graded according to the NCI-CTCAE v4.0 classifications. Quality of life (QoL) Is evaluated | — |
Countries
France
Contacts
Public ContactProject Manager
Fédération Francophone de Cancérologie Digestive
Outcome results
None listed