Atezolizumab in combination with Beva in advanced CRC with MSI-like molecular signature

Phase 1

• Conditions: Colorectal carcinoma; Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 21.0Level: PTClassification code 10061451Term: Colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2016-002001-19-IT
• Lead Sponsor: VALL D'HEBRON INSTITUTE OF ONCOLOGY (VHIO)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-08
• Last Update Posted: 24 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

· 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

Exclusion Criteria

· 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
breast.
· 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 associated with antiphospholipid syn

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified