For patients with advanced/metastatic gastric adenocarcinomas in progression MedDRA version: 21.1 Level: LLT Classification code 10071114 Term: Metastatic gastric adenocarcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Avastin
Product Name: Bevacizumab
Product Code: L01XC07
Pharmaceutical Form: Concentrate and solvent for solution for infusion
Product Name: ipatasertib 100mg
Product Code: RO5532961
Phar
Sponsors
Hospices Civils de Lyon
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Histologically and/or cytologically documented recurrent advanced/metastatic gastric adenocarcinomas previously treated with a platinum and fluoropyrimidine-based regimen. - Patients older than 18 years - Patients with Eastern Cooperative Oncology Group (ECOG) performance status = 2 - Patients must have documented disease progression - Patients who have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 - Accessible tumor lesion (primitive lesion or metastasis) for trial dedicated tumor biopsy. - Left ventricular ejection fraction (LVEF) = 50% by echocardiogram (echo) or multigated acquisition (MUGA) scan within 28 days before day 1 of treatment. - Child-Pugh class A - Patients must have normal organ and marrow function: o Absolute neutrophil count = 1,000/µL, platelets = 75,000/µL, hemoglobin = 9 g/dL o Total bilirubin = 1.5 ULN except subject with documented Gilbert's syndrome, AST(SGOT)/ALT(SGPT) = 2.5 × institutional ULN, Serum alkaline phosphatase = 2.5 x ULN. Patients with bone metastases: alkaline phosphatase = 5 x ULN. o Albumin > 2.5 mg/dL. o Glomerular filtration rate = 60 mL/min as determined by the CKD-EPI equation (or reference methodology such as Iohexol or isotopic technic). o Urine dipstick for proteinuria =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Patients pretreated with one of the experimental drugs, or with ramucirumab. - Uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure-New York Heart Association Class III or IV, active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, gastric or duodenal ulceration diagnosed within the previous 6 months, chronic liver or renal disease, or severe malnutrition. - Current peripheral neuropathy of Grade = 3 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.5.0 - Active, second potentially life-threatening cancer - Other malignancy within the last 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS). Patient with a history of localized malignancy diagnosed over 5 years ago may be eligible provided he completed her adjuvant systemic therapy and remains free of recurrent or metastatic disease. - Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement • Any chronic skin condition that does not require systemic therapy • Patients without active disease in the last 5 years may be included but only after consultation with the study physician - Major surgery within 28 days before cycle 1, day 1 - Active infection requiring iv antibiotics at day 1 of cycle 1 - Medical condition that requires chronic systemic steroid therapy or on any other form of immunosuppressive medication. For example, patients with autoimmune disease that requires systemic steroids or immunosuppression agents should be excluded. Replacement therapy (eg., thyroxine, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. - Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest - Patient is positive for the human immunodeficiency virus (HIV), HepBsAg, or HCV RNA. - Live vaccine within 28 days of planned start of study therapy - History of abdominal fistula, gastrointestinal perforation and/or intra-abdominal abscess within the previous 6 months - History of Type I or Type II diabetes mellitus requiring insulin - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - Known hypersensitivity to any of the components of atezolizumab, bevacizumab or ipatasertib - Participation in other interventional clinical research that may interfere with the experimental drugs efficacy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of personalized targeted immunotherapy combinations in recurrent advanced/metastatic gastric carcinoma patients, assessed by the objective response rate (ORR). ;Secondary Objective: -To assess other efficacy parameters of personalized targeted immunotherapy combinations in recurrent advanced/recurrent metastatic gastric carcinoma patients with survival analyses (PFS, OS) -To assess the safety of personalized targeted immunotherapy combinations in metastatic/advanced gastric carcinoma patients, assessed by NCI-CTCAE. ;Primary end point(s): Objective response rate, using iRECIST, defined as the percentage of patients experiencing a complete response or a partial response, as their best tumor responses during the whole treatment period.;Timepoint(s) of evaluation of this end point: The whole treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Progression-free survival evaluated according to iRECIST criteria. - Overall survival. - Toxicity using NCI-CTCAE v5.0. - Translational research: tumor immune gene expression (inflamed, excluded, desert), tumor mutational load and circulating DNA mutational load, kinetics of circulating hPG80, gut microbiome flora. ;Timepoint(s) of evaluation of this end point: The whole treatment period or at the end of treatment | — |
Countries
France
Contacts
Public ContactIUNG Annie
Hospices Civils de Lyon
Outcome results
None listed