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Report for Clinical Trial NCT04034459

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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

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.

NCT04034459 Metastatic Colorectal Cancer
MeSH:Colorectal Neoplasms
HPO:Neoplasm of the large intestine

6 Interventions

Name: Bevacizumab

Description: Bevacizumab 5 mg/kg BW iv over 30 to 90* min day 1
Type: Drug
Group Labels: 1

FOLFOXIRI plus bevacizumab

Name: Irinotecan

Description: Irinotecan 150 mg/m² iv, 30 - 90 min. day 1
Type: Drug
Group Labels: 2

FOLFOXIRI plus bevacizumab FOLFOXIRI plus cetuximab

Name: Folinic acid

Description: Folinic acid (racemic) 400 mg/m² iv, 120 min. day 1
Type: Drug
Group Labels: 2

FOLFOXIRI plus bevacizumab FOLFOXIRI plus cetuximab

Name: Oxaliplatin

Description: Oxaliplatin 85mg/m² day 1
Type: Drug
Group Labels: 2

FOLFOXIRI plus bevacizumab FOLFOXIRI plus cetuximab

Name: 5-FU

Description: 5-FU 3000 mg/m² iv over 48 h days 1-2
Type: Drug
Group Labels: 2

FOLFOXIRI plus bevacizumab FOLFOXIRI plus cetuximab

Name: Cetuximab

Description: 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
Type: Drug
Group Labels: 1

FOLFOXIRI plus cetuximab


Primary Outcomes

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

Measure: Overall Response Rate (ORR)

Time: up to 48 months

Secondary Outcomes

Description: Investigation of progression-free survival (PFS) from randomisation

Measure: Progression Free Survival (PFS)

Time: up to 60 months

Description: Investigation of overall survival (OS) from randomisation

Measure: Overall Survival (OS)

Time: up to 60 months

Description: Investigation of early tumour shrinkage (ETS)

Measure: Investigation of Early Tumour Shrinkage (ETS) as early-on-Treatment predictor for treatment

Time: up to 48 months

Description: Investigation of depth of response (DpR)

Measure: Investigation of Depth of Response (DpR) to define nadir for tumour response.

Time: up to 48 months

Description: 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)

Measure: Investigation of Molecular Biomarkers for Prediction of an Anti-EGFR Treatment

Time: up to 48 months

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

Measure: Prospective Analysis of Tumour Marker Level Evolution (CEA and CA 19-9)

Time: up to 48 months

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

Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

Time: up to 48 months

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 V600E

Inclusion Criteria: - Histologically confirmed UICC stage IV adenocarcinoma of the colon or rectum with metastases (metastatic colorectal cancer [mCRC]); metastases primarily non-resectable or surgery refused by the patient - RAS wild-type tumour status (KRAS and NRAS exons 2, 3, 4) (proven in the primary tumour or metastasis) - BRAF-mutant (V600E) tumour (proven in the primary tumour or metastasis) - Age ≥18 years - ECOG performance status 0-1 - Patients suitable for chemotherapy administration - Patient's written declaration of consent obtained - Estimated life expectancy > 3 months - Presence of at least one measurable lesion according to the RECIST 1.1 - criteria (chest X-ray in two planes or chest CT and abdominal CT 4 weeks or less before randomisation) - Primary tumour tissue available and patient consents to storage and molecular and genetic profiling of the tumour material. --- V600E ---

- Absent or restricted legal capacity Inclusion Criteria: - Histologically confirmed UICC stage IV adenocarcinoma of the colon or rectum with metastases (metastatic colorectal cancer [mCRC]); metastases primarily non-resectable or surgery refused by the patient - RAS wild-type tumour status (KRAS and NRAS exons 2, 3, 4) (proven in the primary tumour or metastasis) - BRAF-mutant (V600E) tumour (proven in the primary tumour or metastasis) - Age ≥18 years - ECOG performance status 0-1 - Patients suitable for chemotherapy administration - Patient's written declaration of consent obtained - Estimated life expectancy > 3 months - Presence of at least one measurable lesion according to the RECIST 1.1 - criteria (chest X-ray in two planes or chest CT and abdominal CT 4 weeks or less before randomisation) - Primary tumour tissue available and patient consents to storage and molecular and genetic profiling of the tumour material. --- V600E ---



HPO Nodes


HPO: