Neoplasms

All Conditions

Neoplasms, Second Primary

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Irinotecan

Leucovorin

Fluorouracil

Levoleucovorin

Folic Acid

Panitumumab

Vitamin B Complex

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antidotes

Protective Agents

Trace Elements

Antineoplastic Agents, Immunological

Folinic Acid

Folate

Vitamin B9

Panitumumab 6 mg/kg BW as 60-min i.v. infusion\* D1

\*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes.

Followed by FOLFIRI regimen

* Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1
* Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1
* 5-FU 400 mg/m² BSA, bolus, D1
* 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2

q day 14

Panitumumab 6 mg/kg BW as 60-min i.v. infusion\* D1

\*If the 1st infusion is well tolerated, all subsequent infusions can be applied over 30-60 minutes.

Irinotecan 180 mg/m² BSA i.v., 30 - 90 min D1

Folinic acid (racemic) 400 mg/m²BSA i.v., 120 min D1

Folinic acid

5-FU 400 mg/m² BSA, bolus, D1 5-FU 2400 mg/m² BSA i.v. infusion over a period of 46 h D1-2

5-FU

Volker Heinemann, Prof. Dr.

Sebastian Stintzing, Prof. Dr.

Dominik Modest, PD Dr.

The present hypothesis is that anti-EGFR agents are active in tumors with low-level RAS mutation when the majority of tumor cells is still sensitive. While response rate may be high and may reflect sensitivity to anti-EGFR agents, PFS is anticipated to be shorter than in RAS wild-type patients due to the faster development of resistance when sensitive cells are eradicated and when the RAS-mutant anti-EGFR resistant clones become predominant.

The characteristics of low-level RAS mutant tumors would be:

* Objective response rate (ORR) high (reflecting the sensitive clone)
* Progression-free survival (PFS) short (reflecting the more rapid outgrowth of RAS mutant clones)

Optimal Anti-EGFR Treatment of mCRC Patients With Low-Frequency RAS Mutation

FIRE-5 -Study: Optimal Anti-EGFR Treatment of mCRC Patients With Low-Frequency RAS Mutation

As primary endpoint ORR according to RECIST 1.1 will be evaluated separately for each arm of patients with defined low-frequency RAS mutation

PFS, separately for each arm of patients with defined low-frequency RAS mutation

OS, separately for each arm of patients with defined low-frequency RAS mutation

ETS, separately for each group of patients with defined low-frequency RAS mutation

DpR, separately for each arm of patients with defined low-frequency RAS Mutation.

Amgen

ClinAssess GmbH

Ludwig-Maximilians - University of Munich

Director of the CCC-Munich at the LMU Munich

Digestive System Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Oxaliplatin

Bevacizumab

Cetuximab

Angiogenesis Inhibitors

Growth Inhibitors

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

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

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
Optimal Anti-EGFR Treatment of mCRC Patients With Low-Frequency RAS Mutation	NCT04034173	Treatment Relat...	Panitumumab Irinotecan Folinic acid 5-FU	18 Years -	Ludwig-Maximilians - University of Munich
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
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

Spots Global Cancer Trial Database for fire

Every month we try and update this database with for fire 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 fire

Every month we try and update this database with for fire 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 fire 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.