Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Oxaliplatin

Bevacizumab

Atezolizumab

Leucovorin

Fluorouracil

Irinotecan

Levoleucovorin

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Immune Checkpoint Inhibitors

Folinic Acid

Folate

Vitamin B9

(to be repeated every 2 weeks for a maximum of 8 cycles) Bevacizumab 5 mg/kg iv over 30 minutes day 1, followed by Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours day 1, followed by 5-fluorouracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1 (to be repeated every 2 weeks for a maximum of 8 cycles)

If no progression occurs during FOLFOXIRI plus bev, patients will receive maintenance 5-FU/LV plus bev at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus bev will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.

The prosecution of bev until disease progression is recommended also if 5-FU is interrupted because of adverse events, patient's refusal or investigator's choice.

Atezolizumab 840 mg iv over 30 minutes(60 minutes at the first infusion) day 1 followed by Bevacizumab 5 mg/kg iv over 30 minutes day 1, followed by Irinotecan 165 mg/sqm iv over 60 minutes day 1, followed by Oxaliplatin 85 mg/sqm iv over 2 hours day 1, in two-way with L-Leucovorin 200 mg/sqm iv over 2 hours day 1, followed by 5-fluorouracil 3200 mg/sqm 48 h-continuous infusion, starting on day 1 (to be repeated every 2 weeks for a maximum of 8 cycles)

If no progression occurs during FOLFOXIRI plus bev plus atezolizumab, patients will receive maintenance 5-FU/LV plus bev plus atezolizumab at the same dose used at the last cycle of the induction treatment. 5-FU/LV plus bev plus atezolizumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.

The prosecution of bev and atezolizumab until disease progression is recommended also if 5-FU is interrupted because of adverse events, patient's refusal or investigator's choice.

L-Leucovorin

5-fluorouracil

840 mg iv over 30 minutes (60 minutes at the first infusion) day 1

The scope of this study is to evaluate the efficacy of the addition of atezolizumab to FOLFOXIRI plus bevacizumab as first line treatment of patients with metastatic colorectal cancer in terms of Progression Free Survival.

This is a prospective, open-label, multicentric phase II randomized in a 1:2 ratio trial in which patients initially unresectable and previously untreated mCRC will receive induction treatment with FOLFOXIRI plus bev up to 8 cycles followed by maintenance with 5-FU/LV plus bev until disease progression, unacceptable toxicity or patient's refusal (arm A) versus FOLFOXIRI plus bev plus atezolizumab up to 8 cycles followed by maintenance with 5-FU/LV plus bev plus atezolizumab until disease progression, unacceptable toxicity or patient's refusal (arm B). If disease progression does not occur during induction, at the treating physician's discretion, the reintroduction after progression of the same induction treatment (up to 8 cycles) according to randomization arm, followed by maintenance until disease progression, unacceptable toxicity or patient's refusal, is recommended.

The third- and subsequent lines of treatment will be at investigators' choice.

prospective, open-label, multicentric phase II randomized in a 1:2 ratio

FOLFOXIRI + Bev + Atezo vs FOLFOXIRI + Bev as First-line Treatment of Unresectable Metastatic Colorectal Cancer Patients

Randomized Phase II Study of FOLFOXIRI Plus Bevacizumab Plus Atezolizumab Versus FOLFOXIRI Plus Bevacizumab as First-line Treatment of Unresectable Metastatic Colorectal Cancer Patients.

Progression-free survival is defined as the time from randomization to the first documentation of objective disease progression or death due to any cause, whichever occurs first.

Overal Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing any adverse event, according to National Cancer Institute Common Toxicity Criteria (version 4.0), during the induction and the maintenance phases of treatment.

Toxicity Rate is defined as the percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 4.0), during the induction and the maintenance phases of treatment.

Objective Response Rate (ORR) is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria, during the induction and the maintenance phases of treatment. The determination of clinical response will be based on investigator reported measurements. Responses will be evaluated every 8 weeks.

Immuno-related Objective Response Rate (irORR) is defined as the percentage of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to immune-modified RECIST criteria, during the induction and the maintenance phases of treatment. The determination of clinical response will be based on investigator reported measurements. Responses will be evaluated every 8 weeks.

Early Objective Response Rate (EOR) is defined as the percentage of patients, relative to the total of the enrolled subjects, achieving a ≥ 20% decrease in the sum of diameters of RECIST target lesions at week 8 compared to baseline.

Deepness of Response (DoR) is defined as the relative change in the sum of longest diameters of RECIST target lesions at the nadir, in the absence of new lesions or progression of non-target lesions, when compared with baseline.

R0 Resection Rate is defined as the percentage of patients, relative to the total of enrolled subjects, undergoing secondary R0 resection of metastases. Secondary R0 surgery is defined as microscopically margin free complete surgical removal of all residual disease, performed during treatment or after its completion, allowed by tumoral shrinkage and/or disappearance of one or more lesions.

Progression Free Survival 2 (PFS2) is defined as beginning with randomization and ending with the first of the following events: a) death; b) disease progression according to RECIST 1.1 criteria on any treatment given after 1st progression. For patients that will not receive any treatment within 3 months after 1st progression, PFS2 will be equal to PFS. Censoring rules for PFS2 will be: end of study without PD, loss at follow-up. Curative surgery for metastasis will not result in censoring for PFS2.

PFS2 will be analyzed both in the intention-to-treat population (whichever 2nd-line treatment will be adopted) and in the per-protocol population.

2nd-Progression free survival (2nd-PFS) is defined as the time from the beginning of the second-line treatment to the documentation of objective disease progression according to RECIST 1.1 criteria or death due to any cause, whichever occurs first. 2nd-PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive, on study and 2nd-progression free at the time of the analysis. 2nd-PFS will be analyzed both in the intention-to-treat population (whichever 2nd-line treatment will be adopted) and in the per-protocol population.

Spots Global Cancer Trial Database for FOLFOXIRI + Bev + Atezo vs FOLFOXIRI + Bev as First-line Treatment of Unresectable Metastatic Colorectal Cancer Patients

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