A phase II open-label study with the anti-PD-L1 Atezolizumab monoclonal antibody in combination with Bevacizumab in patients with advanced chemotherapy resistant colorectal cancer and MSI-like molecular signature

VHIO0 个研究点目标入组 58 人开始时间: 2017年6月30日最近更新: 2021年8月2日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: VHIO
入组人数: 58

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•· Written informed consent must be given according to ICH/GCP and national/local regulations.
•· Histological or cytological proof of metastatic CRC.
•· Disease progression or relapse after at least one line of treatment for advanced CRC with a fluoropyrimidine containing chemotherapy as single agent or in combination (combinations with oxaliplatin, irinotecan, bevacizumab, and cetuximab or panitumumab are allowed).
•· Written documentation of positivity for MSI-like gene signature as determined by Agendia test.
•· Unresectable disease, with at least one measurable lesion according to RECIST 1.1.
•· Age = 18 years.
•· WHO performance status of 0-1.
•· Ability and capacity to comply with study and follow-up procedures.
•· Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 28 calendar days prior to the first study treatment:
•- ANC > 1.5 x 109/L (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
•- WBC counts > 2500/µL
•- Platelet count > 100,000/ µL (without transfusion within 2 weeks prior to Cycle 1, Day 1)
•- Hemoglobin > 9.0 g/dL
•- AST, ALT, and alkaline phosphatase < 2.5 x ULN, with the following exceptions:
•i Patients with documented liver metastases: AST and ALT < 5 x ULN
•ii Patients with documented liver or bone metastases: alkaline phosphatase < 5 x ULN
•- Bilirubin <1.5 x ULN. Patients with known Gilbert disease who have serum bilirubin level < 3 x ULN may be enrolled.
•- PT and PTT <1.5 x ULN, unless on a stable dose of warfarin
•- Serum albumin > 2.5 g/dL
•- Creatinine clearance > 30 mL/min (Cockcroft-Gault formula or based on 24-hour urine collection)
•- Protein < 2+ on dipstick urinalysis or = 1.0 g in a 24-hour urine collection. All patients with =2+ protein on dipstick urinalysis at baseline must undergo a 24-hour urine collection for protein.
•· Women of child bearing potential (WOCBP) must have a negative serum pregnancy test before registration.
•· Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last bevacizumab treatment (for women and men) and 5 months
•after the last atezolizumab treatment (for women) . A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly.
•· Female subjects who are breast feeding should discontinue nursing before trial registration and until 6 months after the last bevacizumab treatment and 5 months after the last atezolizumab treatment.
•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 35
•F.1.3 Elderly (>=65 years) yes
•F.1.3.1 Number of subjects for this age range 23

排除标准

•· Any treatment with investigational drugs within 28 d prior to Cycle 1, Day 1.
•· Previous cytotoxic agent within 14 d of planed treatment initiation.
•· Active or untreated CNS metastases as determined by computed CT or MRI
•· Radiotherapy within 14 d prior to Cycle 1, Day 1.
•· Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
•· Previous (within the last 5 y) or concurrent malignancies, with the exception of those treated with expected curative outcome as cone-biopsied in situ carcinoma of the cervix, basal cell carcinoma of the skin, localized prostate cancer or ductal carcinoma in situ of the
•· Life expectancy of < 12 w.
•· History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
•· Positive test for HIV.
•· Active hepatitis B or hepatitis C.
•· Active tuberculosis.
•· Severe infections within 4 w prior to Cycle 1, Day 1.
•· Infection within 2 w prior to Cycle 1, Day 1.
•· Received therapeutic oral or IV antibiotics within 2 w prior to Cycle 1, Day 1.
•· Significant cardiovascular or cerebrovascular disease
•· Major surgical procedure within 28 d prior to cycle 1, day 1, or planned procedure or surgery during the study.
•· Prior allogeneic stem cell or solid organ transplant.
•· Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
•· Prior treatment with CD137 agonists, anti-CTLA-4, anti-PD-1, or anti-PD-L1 therapeutic antibody or immune-related pathway-targeting agents.
•· Current or recent use of dipyridamole, ticlopidine, clopidogrel, or cilostazol .
•· Unstable dose in the last 2 w prior to the first study treatment of prophylactic or therapeutic low molecular-weight heparin, direct thrombin inhibitors, or warfarin. Stable dose is permitted where appropriate anticoagulation indices are stable.
•· Inadequately controlled hypertension.
•· Prior history of hypertensive crisis or hypertensive encephalopathy.
•· Significant vascular disease within 6 m prior to Cycle 1, Day 1.
•· Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the bevacizumab or atezolizumab formulation.
•· Evidence of bleeding diathesis or clinically significant coagulopathy.
•· Patients with history of pulmonary hemorrhage/hemoptysis within 6 m prior to Cycle 1, Day 1.
•· Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 calendar days prior to the first dose of bevacizumab.
•· History of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 m prior to Cycle 1, Day 1.
•· Clinical signs or symptoms of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding.
•· Evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
•· Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture.
•· History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis ass

研究者

发起方

VHIO

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