Study Evaluating Biomarkers in Patients With Colorectal C... | NCT01276379

NCT01276379

ID	Type	Description	Link
2010-019236-12	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
FOLFIRI (m) or FOLFOX-6 (m) + cetuximab	Experimental	FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy.	Drug: FOLFIRI (m) Drug: FOLFOX-6 (m) Drug: Cetuximab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
FOLFIRI (m)	Drug	FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression Free Survival	Measurements according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan. Two groups will be defined based on the score built from the proposed clinical variables and biomarkers. Instead of a binomial distribution, a Log-rank method has been used to calculate the sample size in order to include all the incidents during the follow-up. Expecting a minimum 20% difference (60 vs. 40%) on PFS at 12 months between groups and with the following assumptions: Alpha error (bilateral): 5% Beta error: 20% Results are reported by subgroups to compare outcome measure according to BRAF mutation. All patients belong to same treatment/study arm.	4 years

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival	Measured as time in months from start of study treatment to death or lost to follow up. Results are reported by subgroups to compare outcome measure according to BRAF mutation. All patients belong to same treatment/study arm.	4 years
Response Duration

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, age ≥ 18 years
Able to sign an informed consent form
Advanced and/or metastatic colorectal cancer
Colorectal cancer with KRAS wild type genotype
At least one unidimensionally measurable lesion according to RECIST criteria (1.1 revised) (to be assessed ≤ 28 days prior to the study treatment)
All patients with the following features will be included:
1. Progression free survival > 6 months after adjuvant treatment +/- radiotherapy
2. "De novo" diagnosis of the disease
Performance ECOG status of 0-2
Life expectancy ≥ 3 months
Adequate bone marrow function: neutrophils ≥1,5 x 10^9/L; platelets ≥ 100 x 10^9/L; hemoglobin ≥9 g/dL.
Adequate liver, renal and hematological function as follows:
1. Adequate liver function: SGOT and SGPT 2.5 x ULN (5 x ULN in case of hepatic metastasis). Total bilirubin < 1,5 x ULN. Alkaline phosphatase 2,5 x LSN (5 x ULN if hepatic metastasis or 10 x ULN if bone metastasis)
2. Creatinine clearance or creatinine clearance during 24 hours ≥ 50 mL/min
3. Magnesium ≥ LLN, calcium ≥ LLN

Exclusion Criteria:

PS > 2 or elderly patients with fragility criteria
Previous surgery for metastasis
Previous systemic treatment for the metastatic colorectal cancer
Previous treatment with antibodies anti-EGFR or treatment with small-molecule EGFR tyrosine kinase inhibitors or EGFR signal transduction inhibitors. Subjects who suspend their first dose due to a reaction to the infusion can participate
Central nervous system metastasis (except: treated subjects with asymptomatic CNS metastasis who have not received steroids within the 30 days prior to inclusion)
Prior malignant tumor in the last 5 years, except: basal cell carcinoma of the skin or pre-invasive cervical cancer
Unresolved toxicities from a prior systemic treatment which do not qualify the patient for inclusion
Presence of peripheral neuropathy (degree > 1 in the ctc version 3.0) and serious nonhealing wound, ulcer, or bone fracture
Hormonal treatment, immunotherapy or experimental or approved antibodies/proteins ≤ 30 days before the inclusion
Uncontrolled serious cardiovascular disease or: congestive cardiac failure NYHA lll or lV, unstable angina pectoris, myocardial infarction precedents in the past 12 months, significant arrhythmias
Interstitial pneumonitis or pulmonary fibrosis precedents, or interstitial pneumonitis or pulmonary fibrosis signs on the thoracic CT-scan
Treatment for systemic infection within the 14 days prior to treatment
Acute/subacute intestinal occlusion and/or active inflammatory bowel disease or any other bowel disease producing chronic diarrhea
Precedent of Gilbert's syndrome or dihydropyrimidine dehydrogenase deficiency
Precedent of any disease which can increase the risks associated to the participation in the study or interfere in the study results
Known positive test for the following infections: HIV, Hepatitis C + abnormal liver enzymes values, active chronic Hepatitis B (except Hepatitis C seropositive with normal liver enzymes)
All concurrent diseases which can increase the toxicity risk
The individual presents a disorder of any kind which jeopardizes their ability to give their written consent form and/or fulfill the study procedures
Any investigational agent within 30 days before enrolment
Pregnant or breastfeeding woman, or planning to get pregnant within the 6 months after treatment
Surgery (excluding the diagnostic biopsy or placing of a central venous catheter)
Woman or man of childbearing potential not consenting to use adequate contraceptive precautions during the study and 6 months after de last administration for women, and 1 month for men
Unability to fulfill the study requirements by the patients
Psychological, family, sociological or geographical conditions that may interfere with the fulfillment of the study protocol and the follow-up calendar

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Jesús García Foncillas, MD	Grupo Espanol Multidisciplinario del Cancer Digestivo	Study Chair
Xavier García-Albeniz, MD	Grupo Espanol Multidisciplinario del Cancer Digestivo	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Hospital Provincial de Castellón		Castellon	Castellón		Spain
Hospital Son Espases

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35100697	Derived	Maurel J, Alonso V, Escudero P, Fernandez-Martos C, Salud A, Mendez M, Gallego J, Rodriguez JR, Martin-Richard M, Fernandez-Plana J, Manzano H, Mendez JC, Zanui M, Falco E, Gil-Raga M, Aparicio J, Feliu J, Garcia-Albeniz X, Torres F, Rojo F, Bellosillo B, Mendiola M, Fernandez V, Reig O, Claes B, Maertens G, Sablon E, Jacobs B, Montagut C. Clinical Impact of Circulating Tumor RAS and BRAF Mutation Dynamics in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy Plus Anti-Epidermal Growth Factor Receptor Therapy. JCO Precis Oncol. 2019 Dec;3:1-16. doi: 10.1200/PO.18.00289.
31235483

Label	URL
GEMCAD group	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 23, 2010	Jun 11, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Arm/Group Information

ID	Title	Description
BG000	WT BRAF - FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	Patients with a determination of BRAF status and presence of Wild type (WT) BRAF gen. FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.
BG001	Mutant BRAF - FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	Patients with a determination of BRAF status and presence of a mutation in the BRAF gen. FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00062± 10.5 BG00167± 7.4 BG00265± 9

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00046 BG0017 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Spain

Title	Measurements
	BG000161 BG00120 BG002

Stage

The stage of a cancer describes the size and spread of a tumour:

stage I - The cancer has grown through the mucosa and has invaded the muscular layer of the colon or rectum.

stage II - The cancer has grown through the wall of the colon or rectum stage III - The cancer has grown through the inner lining or into the muscle layers of the intestine. It has spread to lymph nodes stage IV - The cancer has spread to a distant part of the body

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Stage I	BG0001 BG001

Primary location

Part of the colon where the primary tumor was located

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Ascending colon	BG00023 BG0019 BG002

Surgery of the primary tumor

Percentage of patients that had surgery for their primary colorectal tumor

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00091 BG00110 BG002

Performance Status (PS)

Eastern Cooperative Oncology Group (ECOG) performance status. ECOG scale measures the performance status of a patients. It ranges from 0 (fully active, able to carry on all pre-disease performance without restriction) to 5 (death).

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
ECOG 0	BG000112 BG001

Number of metastatic organs

Percentage of patients presenting metastasis in one or more distant organs. The number of patients with 1,2, 3 or more than 4 affected organs are reported

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
1	BG00087 BG0017

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Progression Free Survival

Measurements according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan. Two groups will be defined based on the score built from the proposed clinical variables and biomarkers. Instead of a binomial distribution, a Log-rank method has been used to calculate the sample size in order to include all the incidents during the follow-up. Expecting a minimum 20% difference (60 vs. 40%) on PFS at 12 months between groups and with the following assumptions:

Alpha error (bilateral): 5% Beta error: 20% Results are reported by subgroups to compare outcome measure according to BRAF mutation. All patients belong to same treatment/study arm.

Evaluable population

Posted

Median

95% Confidence Interval

Months

4 years

ID	Title	Description
OG000	WT BRAF - FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	Patients with a determination of BRAF status and presence of Wild type (WT) BRAF gen. FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.
OG001	Mutant BRAF - FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	Patients with a determination of BRAF status and presence of a mutation in the BRAF gen. FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.

Units	Counts
Participants	OG000161 OG00120

Title

Denominators

Categories

Title	Measurements
	OG00011.4(9.9 to 13.1) OG0015.9(3.3 to 7.8)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.004		Hazard Ratio (HR)	2.01			2-Sided	95	1.23	3.29					Superiority

Secondary

Overall Survival

Measured as time in months from start of study treatment to death or lost to follow up.

Results are reported by subgroups to compare outcome measure according to BRAF mutation. All patients belong to same treatment/study arm.

Evaluable population

Posted

Median

95% Confidence Interval

Months

4 years

ID	Title	Description
OG000	WT BRAF - FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	Patients with a determination of BRAF status and presence of Wild type (WT) BRAF gen. FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.
OG001

Secondary

Response Duration

Duration of the partial or total response to the treatment. Evaluation and classification according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors)

Evaluable population

Posted

Median

Full Range

Months

4 years

ID	Title	Description
OG000	FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.

Units	Counts

Secondary

Frequency of Adverse Events

Frequency and type of adverse events (AEs). AEs were coded according to NCI CTCAE V3.0 and classified by frequency, relatedness to study treatment (related/not related) and severity (Grade).

Severity ranges from grade 1 (low intensity) to Grade 5 (max. intensity, death)

Safety population (all patients that received at least one infusion of study treatment)

Posted

Count of Participants

Participants

4 years

ID	Title	Description
OG000	FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.

Secondary

Secondary Biomarkers Analysis

The secondary biomarkers in serum and tumoral tissue will be analysed in order to predict the acquired resistance.

Evaluable population

Posted

Count of Participants

Participants

4 years

ID	Title	Description
OG000	FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.

Units	Counts

Secondary

Tumoral Response

Measurements according to RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors). Main techniques: CT-scan. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR Results are reported by subgroups to compare outcome measure according to BRAF mutation. All patients belong to same treatment/study arm.

Evaluable population

Posted

Count of Participants

Participants

4 years

ID	Title	Description
OG000	WT BRAF - FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	Patients with a determination of BRAF status and presence of Wild type (WT) BRAF gen. FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	FOLFIRI (m) or FOLFOX-6 (m) + Cetuximab	FOLFOX/FOLFIRI + cetuximab 500mg/m2 bi-weekly for 6 months, then bi-weekly cetuximab as monotherapy. FOLFIRI (m): FOLFIRI (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Irinotecan 180 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2), in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. FOLFOX-6 (m): FOLFOX6 (m) chemotherapy will be administered on day 1 of each 14-days-cycle. The administered doses will be: Oxaliplatin 85 mg/m2 in infusion i.v., 120 minutes, on day 1 of each cycle. l-Leucovorin 200 mg/m2 (or d,l-leucovorin 400 mg/m2) in infusion i.v., 120 minutes, on day 1. One bolus i.v. (2-4 minutes) of 400 mg/m2 of 5-FU on day 1. 5-FU in continuous infusion (2400 mg/m2) administered through an ambulatory pump during 46-48 hours. Cetuximab: - 500 mg/m2 i.v. Every 2 weeks.	136	218	173	218	198	218

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Alopecia	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0004 events4 affected218 at risk
Anemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0004 events4 affected218 at risk
Anorexia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0002 events2 affected218 at risk
Ascites	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected218 at risk
Asthenia	General disorders	Non-systematic Assessment	EG00019 events19 affected218 at risk
Diarrhoea	Gastrointestinal disorders	Non-systematic Assessment	EG00028 events28 affected218 at risk
Pain	General disorders	Non-systematic Assessment	EG0002 events2 affected218 at risk
Abdominal pain	Gastrointestinal disorders	Non-systematic Assessment	EG0003 events3 affected218 at risk
Edema	General disorders	Non-systematic Assessment	EG0001 events1 affected218 at risk
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG0002 events2 affected218 at risk
Fever	General disorders	Non-systematic Assessment	EG0001 events1 affected218 at risk
Fistula	Gastrointestinal disorders	Non-systematic Assessment	EG0007 events7 affected218 at risk
Hepatic toxicity	Hepatobiliary disorders	Non-systematic Assessment	EG0003 events3 affected218 at risk
Infections	Infections and infestations	Non-systematic Assessment	EG0009 events9 affected218 at risk
Leucocytopenia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0004 events4 affected218 at risk
Mucositis	Gastrointestinal disorders	Non-systematic Assessment	EG00014 events14 affected218 at risk
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG0009 events9 affected218 at risk
Neuropathy	Nervous system disorders	Non-systematic Assessment	EG0005 events5 affected218 at risk
Neutropenia	Blood and lymphatic system disorders	Non-systematic Assessment	EG00053 events53 affected218 at risk
Febrile neutropenia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0005 events5 affected218 at risk
Intestinal obstruction	Gastrointestinal disorders	Non-systematic Assessment	EG00010 events10 affected218 at risk
Ocular alterations non otherwise specified (NOS)	Eye disorders	Non-systematic Assessment	EG0001 events1 affected218 at risk
paresthesia	Nervous system disorders	Non-systematic Assessment	EG0005 events5 affected218 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0003 events3 affected218 at risk
Alergic reaction	Immune system disorders	Non-systematic Assessment	EG0007 events7 affected218 at risk
Skin reaction	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG00029 events29 affected218 at risk
rectal bleeding	Gastrointestinal disorders	Non-systematic Assessment	EG0001 events1 affected218 at risk
Hand-foot syndrome	General disorders	Non-systematic Assessment	EG0001 events1 affected218 at risk
Transaminitis	Hepatobiliary disorders	Non-systematic Assessment	EG0002 events2 affected218 at risk
Cardiac disorders NOS	Cardiac disorders	Non-systematic Assessment	EG0002 events2 affected218 at risk
Metabolic disorders NOS	Metabolism and nutrition disorders	Non-systematic Assessment	EG0006 events6 affected218 at risk
Gastrointestinal disorders NOS	Gastrointestinal disorders	Non-systematic Assessment	EG0005 events5 affected218 at risk
General and site reactions NOS	General disorders	Non-systematic Assessment	EG0002 events2 affected218 at risk
Muscolosqueletal disorders NOS	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0005 events5 affected218 at risk
Ocular disorders NOS	Eye disorders	Non-systematic Assessment	EG0003 events3 affected218 at risk
Urinary disorders NOS	Renal and urinary disorders	Non-systematic Assessment	EG0004 events4 affected218 at risk
Respiratory disorders NOS	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0006 events6 affected218 at risk
Vascular disorders NOS	Vascular disorders	Non-systematic Assessment	EG00010 events10 affected218 at risk
Xerosis	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0008 events8 affected218 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Alopecia	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG00029 events29 affected218 at risk
Anemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG00034 events34 affected218 at risk
Anorexia	Metabolism and nutrition disorders	Non-systematic Assessment	EG00027 events27 affected218 at risk
Asthenia	General disorders	Non-systematic Assessment	EG000101 events101 affected218 at risk
Diarrhoea	Gastrointestinal disorders	Non-systematic Assessment	EG00080 events80 affected218 at risk
Dysgeusia	Nervous system disorders	Non-systematic Assessment	EG00022 events22 affected218 at risk
Pain NOS	General disorders	Non-systematic Assessment	EG00021 events21 affected218 at risk
Abdominal pain	Gastrointestinal disorders	Non-systematic Assessment	EG00028 events28 affected218 at risk
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG00040 events40 affected218 at risk
Fever	General disorders	Non-systematic Assessment	EG00025 events25 affected218 at risk
Fistula	Gastrointestinal disorders	Non-systematic Assessment	EG00047 events47 affected218 at risk
Infections NOS	Infections and infestations	Non-systematic Assessment	EG00017 events17 affected218 at risk
Leucopenia	Blood and lymphatic system disorders	Non-systematic Assessment	EG00016 events16 affected218 at risk
Mucositis	Gastrointestinal disorders	Non-systematic Assessment	EG00087 events87 affected218 at risk
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG00060 events60 affected218 at risk
Neuropathy	Nervous system disorders	Non-systematic Assessment	EG00072 events72 affected218 at risk
Neutropenia	Blood and lymphatic system disorders	Non-systematic Assessment	EG00037 events37 affected218 at risk
Paresthesia	Nervous system disorders	Non-systematic Assessment	EG00045 events45 affected218 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Non-systematic Assessment	EG00022 events22 affected218 at risk
Cutaneous reaction	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG000134 events134 affected218 at risk
Mucosa dryness	Gastrointestinal disorders	Non-systematic Assessment	EG00013 events13 affected218 at risk
Transaminitis	Hepatobiliary disorders	Non-systematic Assessment	EG00013 events13 affected218 at risk
Metabolic disorders NOS	Metabolism and nutrition disorders	Non-systematic Assessment	EG00036 events36 affected218 at risk
gastrointestinal disorders	Gastrointestinal disorders	Non-systematic Assessment	EG00040 events40 affected218 at risk
Musculoskeletal disorders NOS	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG00020 events20 affected218 at risk
Ocular disorders NOS	Eye disorders	Non-systematic Assessment	EG00024 events24 affected218 at risk
Psychiatric disorders NOS	Psychiatric disorders	Non-systematic Assessment	EG00012 events12 affected218 at risk
Urinary disorders NOS	Renal and urinary disorders	Non-systematic Assessment	EG00013 events13 affected218 at risk
Respiratory disorders NOS	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG00029 events29 affected218 at risk
Vascular disorders NOS	Vascular disorders	Non-systematic Assessment	EG00012 events12 affected218 at risk
trichomegaly	Congenital, familial and genetic disorders	Non-systematic Assessment	EG00011 events11 affected218 at risk
Xerosis	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG00036 events36 affected218 at risk

ID	Term
D015179	Colorectal Neoplasms
D009362	Neoplasm Metastasis
D009477	Hereditary Sensory and Autonomic Neuropathies

Ancestor Terms

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D009421	Nervous System Malformations
D009422	Nervous System Diseases
D020271	Heredodegenerative Disorders, Nervous System
D019636	Neurodegenerative Diseases
D011115	Polyneuropathies
D010523	Peripheral Nervous System Diseases
D009468	Neuromuscular Diseases
D000013	Congenital Abnormalities
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D030342	Genetic Diseases, Inborn

ID	Term
D002955	Leucovorin
D005472	Fluorouracil
D000077146	Irinotecan
D000077150	Oxaliplatin
D000068818	Cetuximab

Ancestor Terms

ID	Term
D005575	Formyltetrahydrofolates
D013763	Tetrahydrofolates
D005492	Folic Acid
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D003067	Coenzymes
D045762	Enzymes and Coenzymes
D014498	Uracil
D011744	Pyrimidinones
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D002166	Camptothecin
D000470	Alkaloids
D056831	Coordination Complexes
D009930	Organic Chemicals
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

Units	Counts
Participants	OG000218