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

Amino Acids

Capecitabine

Bevacizumab

Oxaliplatin

Imatinib Mesylate

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Dose level I:

Bevacizumab day 1: 7,5 mg/kg body weight Oxaliplatin day 1: 100 mg/m2 Capecitabine days 1-14 bid: 800 mg/m2 Imatinib days 1-21: 300 mg

Repeat on day 22.

Dose level II:

Bevacizumab day 1: 7,5 mg/kg body weight Oxaliplatin day 1: 130 mg/m2 Capecitabine days 1-14 bid: 1000 mg/m2 Imatinib days 1-21: 300 mg

Repeat on day 22.

Oxaliplatin, Capecitabine, Bevacizumab, Imatinib

Ulrich Hacker, PD Dr.

Assessment of safety and toxicity, definition of the dose limiting toxicity (DLT) of the combination therapy consisting of Capecitabine, Oxaliplatin, Bevacizumab and Imatinib.

The monoclonal anti-VEGF antibody bevacizumab has been approved for the treatment of stage IV colorectal cancer. The tyrosine kinase inhibitor imatinib mesylate has been shown to efficiently target PDGF-signalling. Blocking PDGFR-signalling leads to disruption of pericytes from the endothelium and reverses the maturation status thereby enhancing the sensitivity to anti-VEGF therapy.This background forms a rationale for a combined therapeutic PDGF and VEGF inhibition. Since bevacizumab shows best activity when used in combination with chemotherapy, capecitabine and oxaliplatin are included in this protocol. Patients with stage IV colorectal cancer and no prior chemotherapy can enter the study. Patients receive oral imatinib once a day on days 1-21. Oral Capecitabine is given on days 1-14 bid, Oxaliplatin and Bevacizumab are given on day 1. Courses are repeated every 22 days in the absence of disease progression or unacceptable toxicity.

First-line Therapy of Stage IV Colorectal Cancer

A Phase I/II Study of Capecitabine/Oxaliplatin (XELOX) in Combination With Bevacizumab and Imatinib as First-line Treatment of Patients With Stage IV Colorectal Cancer

Roche Pharma AG

Novartis

Sanofi

University of Cologne

PD Dr.

Micronutrients

Hematinics

Vitamins

Leucovorin

Fluorouracil

Irinotecan

Cetuximab

Levoleucovorin

Folic Acid

Vitamin B Complex

Topoisomerase I Inhibitors

Antidotes

Protective Agents

Trace Elements

Folinic Acid

Folate

Vitamin B9

One cycle (cycle duration 14 days) consists of:

* Irinotecan 150 mg/m² iv, 30 - 90 min. day 1
* Folinic acid (racemic) 400 mg/m² iv, 120 min. day 1
* Oxaliplatin 85mg/m² day 1
* 5-FU 3000 mg/m² iv over 48 h days 1-2
* Bevacizumab 5 mg/kg BW iv over 30 to 90\* min day 1 \*1st administration 90 min.; in case of good tolerability, second administration 60 min.; further administrations 30 min.

Repeat administration every 2 weeks for a maximum of 12 cycles

* Dose adaptation at the treating physician's discretion.
* Switch to the recommended maintenance treatment with fluoropyrimidine and bevacizumab after the 8th cycle (following 2nd staging after baseline) is possible at the treating physician's discretion if response according to RECIST 1.1 (CR or PR) has been achieved.

One cycle (cycle duration 14 days) consists of:

* Irinotecan 150 mg/m² iv, 30 - 90 min. day 1
* Folinic acid (racemic) 400 mg/m² iv, 120 min. day 1
* Oxaliplatin 85mg/m² day 1
* 5-FU 3000 mg/m² iv over 48 h days 1-2
* Cetuximab initially 400 mg/m² with infusion rate of ≤5 mg/min., subsequently 250 mg/m² iv with infusion rate of ≤10 mg/min. days 1+8

Repeat administration every two weeks up to a maximum of 12 cycles.

* Dose adaptation at the treating physician's discretion.
* Switch to the recommended maintenance treatment with 5-FU and cetuximab or irinotecan and cetuximab after the 8th cycle (following 2nd staging after baseline) is possible at the treating physician's discretion if response according to RECIST 1.1 (CR or PR) has been achieved.

Bevacizumab 5 mg/kg BW iv over 30 to 90\* min day 1

Irinotecan 150 mg/m² iv, 30 - 90 min. day 1

Folinic acid (racemic) 400 mg/m² iv, 120 min. day 1

Folinic acid

5-FU

Cetuximab initially 400 mg/m² with infusion rate of ≤5 mg/min., subsequently 250 mg/m² iv with infusion rate of ≤10 mg/min. days 1+8

Volker Heinemann, Prof. Dr.

Once randomisation has been completed, the study treatment should be started preferably immediately; at the latest within one week following randomisation.

The patients will be randomised in a ratio of 1:2 to the following two treatment arms.

Patients in both treatment arms will receive standard chemotherapy with FOLFOXIRI as background treatment, which can be de-escalated to FOLFIRI in case of toxicity.

Standard arm A:

The patient will be treated with FOLFOXIRI plus bevacizumab for up to 12 cycles (24 weeks) or until progression (if the latter occurs before completing the 12 cycles). Within the 12 cycles, the FOLFOXIRI plus bevacizumab regimen may be de-escalated, owing to toxicity, to FOLFIRI and bevacizumab at the treating physician's discretion.

After 12 cycles of the study treatment, a switch to a maintenance regimen with a fluoropyrimidine (5-FU infusion or capecitabine) plus bevacizumab, administered until progression occurs, is recommended. The recommended maintenance phase of the study is not part of the study treatment. However, maintenance therapy will be counted as first-line therapy.

Experimental arm B:

The patient will be treated with FOLFOXIRI plus weekly administration of cetuximab for up to 12 cycles (24 weeks) or until progression (if the latter occurs before completing the 12 cycles). Within the 12 cycles, the FOLFOXIRI plus cetuximab regimen may be de-escalated owing to toxicity, to FOLFIRI and cetuximab at the treating physician's discretion.

After 12 cycles, a switch to a maintenance regimen with 5-FU and cetuximab or with irinotecan and cetuximab, administered until progression occurs, is recommended. The recommended maintenance phase of the study is not part of the study treatment. However, maintenance therapy will be counted as first-line therapy.

FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab 1st-line in BRAF-mutated mCRC

Randomised Study to Investigate FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab as First-line Treatment of BRAF-mutated Metastatic Colorectal Cancer

(overall response rate) measured in percentage of all treated patients according to RECIST 1.1 criteria

Investigation of progression-free survival (PFS) from randomisation

Investigation of overall survival (OS) from randomisation

Investigation of early tumour shrinkage (ETS)

Investigation of molecular biomarkers for prediction of sensitivity and secondary resistance of an anti-EGFR treatment with cetuximab (including tumour biopsies and liquid biopsies from blood samples)

Investigation of prospective analysis of tumour marker level evolution (CEA and CA 19-9)

Recording of the safety and tolerability (NCI-CTCAE version 4.03 criteria) of the treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
First-line Therapy of Stage IV Colorectal Cancer	NCT00784446	Stage IV Colore...	Oxaliplatin, Ca...	18 Years -	University of Cologne
FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab 1st-line in BRAF-mutated mCRC	NCT04034459	Metastatic Colo...	Bevacizumab Irinotecan Folinic acid Oxaliplatin 5-FU Cetuximab	18 Years -	Ludwig-Maximilians - University of Munich
First-line Therapy of Stage IV Colorectal Cancer	NCT00784446	Stage IV Colore...	Oxaliplatin, Ca...	18 Years -	University of Cologne
FOLFOXIRI Plus Cetuximab vs. FOLFOXIRI Plus Bevacizumab 1st-line in BRAF-mutated mCRC	NCT04034459	Metastatic Colo...	Bevacizumab Irinotecan Folinic acid Oxaliplatin 5-FU Cetuximab	18 Years -	Ludwig-Maximilians - University of Munich
First-line Therapy of Stage IV Colorectal Cancer	NCT00784446	Stage IV Colore...	Oxaliplatin, Ca...	18 Years -	University of Cologne

Spots Global Cancer Trial Database for aio

Every month we try and update this database with for aio cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for aio

Every month we try and update this database with for aio cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for aio cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.