Neoplasms

Symptoms and General Pathology

All Conditions

Digestive System Diseases

Neoplastic Cells, Circulating

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Oxaliplatin

Bevacizumab

Leucovorin

Fluorouracil

Irinotecan

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

* Bevacizumab 5 mg/kg iv, day 1, followed by
* Oxaliplatin 85 mg/m2 iv administered over a period of 2 hours, day 1, followed by
* 5- Fluorouracil (FU)/Leucovorin (LV), day 1 and 2, as follow:

  * LV 400 mg/m2 iv administered over a period of 2 hours, followed by
  * 5-FU 400 mg/m2 iv bolus, followed by
  * 5-FU 2.400 mg/m2 over 46 h continuous infusion. This treatment will start on day 1 and will be repeated every 2 weeks (1 cycle).

modified FOLFOX6 + bevacizumab

* Bevacizumab 5 mg/kg iv, followed by
* Irinotecan 165 mg/m2 iv administered over a period of 30-90 minutes, followed by
* Oxaliplatin 85 mg/m2 iv administered over a period of 2 hours, followed by
* LV 400 mg/m2 iv administered over a period of 2 hours, followed by
* 5-FU 3,200 mg/m2 for 48 h continuous infusion. This treatment will start on day 1 and will be repeated every 2 weeks (1 cycle).

FOLFOXIRI + Bevacizumab

Eduardo Díaz-Rubio, MD-PhD

Enrique Aranda, MD-PhD

Javier Sastre, MD-PhD

The purpose of the study is to evaluate FOLFOX + bevacizumab versus FOLFOXIRI + bevacizumab as first line treatment of patients with metastatic colorectal cancer not previously treated and with three or more circulating tumoral cells.

Study of 5-Fluorouracil/Leucovorin/Oxaliplatin (FOLFOX) + Bevacizumab Versus 5-Fluorouracil/Leucovorin/Oxaliplatin/Irinotecan (FOLFOXIRI) + Bevacizumab as First Line Treatment of Patients With Metastatic Colorectal Cancer Not Previously Treated and With Three or More Circulating Tumoral Cells

Phase III, Randomized Clinical Trial to Evaluate FOLFOX + Bevacizumab Versus FOLFOXIRI + Bevacizumab as First Line Treatment of Patients With Metastatic Colorectal Cancer Not Previously Treated and With Three or More Circulating Tumoral Cells.

Roche Pharma AG

Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Neoplasm Metastasis

Hematinics

Liver Extracts

Iron-Dextran Complex

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Bevacizumab 5mg/kg + irinotecan\* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles

Irinotecan\* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2800 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle until PD or resectability or to max. 12 cycles

FOLFOXIRI

Yanhong Deng, M.D.

BACKGROUND:

For patients with liver-limited metastatic colorectal cancer (mCRC), complete resection of liver metastases is the only potentially curative treatment. The current goal of medical treatment for colorectal cancer with initially unresectable liver metastases is to maximize the rate of secondary resection and prolong overall survival (OS). A strong correlation was found between response rate and secondary resection rate of metastases, and the triple drugs combination of infusional 5-fluorouracil/leucovorin (5-FU/LV), irinotecan, and oxaliplatin (FOLFOXIRI) was recommended can be used in selected patients with potentially resectable metastases in order to improve response rate and make resection more possible. The addition of a anti-VEGFs monoclonal antibody such as bevacizumab to chemotherapy has been shown to increase response rate, resection rate and improve OS in the first-line treatment of mCRC patients. The efficacy and safety of bevacizumab in addition to triplet drugs were previously tested in OLIVIA trial, the resection rate of liver metastases of 49% was reported, and the response rate was 81%; most common grade 3-4 adverse events was neutropenia. On the basis of such promising results, we conducted the present randomized study to explore whether FOLFOXIRI plus bevacizumab compared with FOLFOXIRI alone as first-line treatment could improve radical resectability in patients with RAS mutation-type, unresectable liver-only metastatic colorectal cancer.

OBJECTIVE:

The primary objective of the FOBULM study is to evaluate the efficacy of FOLFOXIRI plus bevacizumab compared to FOLFOXIRI alone in patients with initially unresectable liver-limited RAS mutation-type mCRC.

Secondary objectives are safety and tolerability of the treatment, efficacy in terms of objective response rate (ORR), OS, progression free survival (PFS), quality of life and an assessment of biomarkers for predictive response and prognosis.

OVERVIEW OF TRIAL DESIGN

This FOCULM trial is a a two-arm, multicenter, open labelled, prospective, randomized phase II studies. Eligible patients with initially unresectable liver-limited mCRC will be randomised 1:1 to receive either FOLFOXIRI plus bevacizumab or FOLFOXIRI alone.

FOLFOXIRI With or Without Bevacizumab as First-line Treatment for Unresectable Liver-only Metastatic Colorectal Cancer Patients With RAS Mutation-type

A Phase II Study to Evaluate the Surgical Conversion Rate in Patients With RAS Mutation-type Receiving FOLFOXIRI +/- Bevacizumab for Unresectable Colorectal Liver-Limited Metastases

Defined as the proportion of patients who had a curative liver treatment following protocol treatment, i.e., liver metastases that can be radical resected with or without ablation with no postoperative evidence of residual malignant disease.

The grade of toxicity will be assessed using the NCI common toxicity criteria, version 4.0.

CR + PR rate will be assessed according to the RECIST version 1.1 guidelines.

Estimated from the date of randomization to death from any cause.

Time measured from the day of randomization to the date of first documented progression, or death from any cause.

Scores according to EORTC QLQ-C30 scoring manual

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of 5-Fluorouracil/Leucovorin/Oxaliplatin (FOLFOX) + Bevacizumab Versus 5-Fluorouracil/Leucovorin/Oxaliplatin/Irinotecan (FOLFOXIRI) + Bevacizumab as First Line Treatment of Patients With Metastatic Colorectal Cancer Not Previously Treated and With Three or More Circulating Tumoral Cells	NCT01640405	Metastatic Colo...	modified FOLFOX... FOLFOXIRI + Bev...	18 Years - 70 Years	Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
FOLFOXIRI With or Without Bevacizumab as First-line Treatment for Unresectable Liver-only Metastatic Colorectal Cancer Patients With RAS Mutation-type	NCT02350530	Metastatic Colo...	FOLFOXIRI + Bev... FOLFOXIRI	18 Years - 70 Years	Sun Yat-sen University

Spots Global Cancer Trial Database for folfoxiri + bevacizumab