folfoxiri plus bevacizumab plus atezolizumab or folfoxiri plus bevacizumab nel carcinoma del colonretto metastatico.

Phase 1

• Conditions: Metastatic Colorectal Cancer; MedDRA version: 21.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-000977-35-IT
• Lead Sponsor: G.O.N.O. - GRUPPO ONCOLOGICO DEL NORD OVEST

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-18
• Last Update Posted: 2 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 201

Inclusion Criteria

•Written informed consent to study procedures and to molecular analyses
•Histologically proven diagnosis of colorectal cancer
•Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease
•At least one measurable lesion according to RECIST1.1 criteria
•Availability of a tumoral sample
•Male or female of 18-75 years of age
•ECOG PS < or = 2 if aged < 71 years, ECOG PS = 0 if aged 71-75 years
•Life expectancy of at least 12 weeks
•Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse
•Neutrophils > 1.5 x 109/L, Platelets >100 x 109/L, Hgb >9 g/dl
•Total bilirubin 1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) <2.5 x UNL (or <5 x UNL in case of liver metastases) alkaline phosphatase <2.5 x UNL (or <5 x UNL in case of liver metastases)
•Creatinine clearance =50 mL/min or serum creatinine 1.25 x UNL
•INR or aPTT ¿1.5 × ULN. Patients who are on therapeutic doses of anti-coagulants are eligible if they are on a stable dose of anti-coagulant for 28 days with stable INR and PTT values.
•Urine dipstick of proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate ¿1 g of protein/24 hr
•Male subjects with female partners of childbearing potential must be willing to use adequate contraception as outlined in Section 5.5 – Contraception, starting with the first dose of study therapy through 6 months after the last dose of bevacizumab and within 5 months after the last dose of atezolizumab.
•Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
•Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 continuous months, are surgically sterile, or are sexually inactive.
•Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 5.5 – Contraception, for the course of the study starting with the first dose of study therapy through 6 months after the last dose of bevacizumab and within 5 months after the last dose of atezolizumab.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
•Will and ability to comply with the protocol

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 134
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 67

Exclusion Criteria

Clinically significant cardiovascular disease
Previous treatment with bevacizumab
Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
Untreated brain metastases or spinal cord compression or primary brain tumours
Pregnant or lactating women
History of autoimmune disease
History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia or evidence of active pneumonitis on screening chest CT scan
Positive test for HIV
Active HBV test or HCV
Active tuberculosis
Prior allogenic bone marrow transplantation or solid organ transplant
Treatment with systemic corticosteroids or other systemic immunosuppressive medications
Known hypersensitivity or allergy to Chinese hamster ovary cell products or any component of the atezolizumab formulation
Administration of a live, attenuated vaccine within 4 weeks prior to start of study treatment or anticipation that such a live attenuated vaccine will be required during the study
Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to start of study treatment
If receiving a RANKL inhibitor (e.g. denosumab), unwilling to adopt alternative treatment such as (but not limited to) bisphosphonates, while receiving atezolizumab.

Study & Design

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