Biomarker Directed Treatment in Metastatic Colorectal Cancer

NCT ID: NCT01703390

Last Updated: 2020-12-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-04
• Study Completion Date: 2020-07-03

Brief Summary

This pilot study is being mounted to assess whether treatment assignment by ERCC-1 gene expression status suggests better clinical results from historical experience in metastatic colorectal cancer (mCRC). In wild type KRAS mCRC patients treated with either FOLFOX or FOLFIRI in combination with cetuximab the median response rate is approximately 60-65%. Biomarker directed treatment in this study may demonstrate that patients with low ERCC-1 treated with FOLFOX and cetuximab, and those with high ERCC-1 treated with FOLFIRI and cetuximab, will improve response rate to 70-75%. KRAS wild type patients will be treated with 6 cycles of one of the following regimens chosen for optimization based on patient characteristics (primary treatment phase). Patients with ERCC-1 < 1.7 relative gene expression of ERCC-1 over ß-actin (ERCC-1 low) will be assigned to treatment with mFOLFOX6 in combination with Cetuximab. Patients with ERCC-1 gene expression > 1.7 relative gene expression of ERCC-1 over over ß-actin (ERCC-1 high) will be assigned to treatment with FOLFIRI in combination with Cetuximab.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancer; mCRC; ERCC-1; ERCC1; AGMT

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ERCC-1 low

modifiedFOLFOX6 + Cetuximab oxaliplatin 85 mg/m2 on day 1, 15 q d29 for 6 cycles folinic acid (FA) 400 mg/m2 on days 1 and 15 and q d29 for 6 cycles fluorouracil (5-FU) 400 mg/m2 bolus day 1 + 2400 mg/m2 46-hour infusion on days 1, 2 and 15, 16 and q d29 for 6 cycles or until unacceptable toxicity Cetuximab will be administered as a 120- minute intravenous infusion at 500 mg/m2 on day 1 then 500 mg/m2 bi-weekly

Group Type: EXPERIMENTAL

modifiedFOLFOX6 + Cetuximab

Intervention Type: DRUG

ERCC-1 high

FOLFIRI + Cetuximab irinotecan 180 mg/m² on day 1, 15 q d29 for 6 cycles folinic acid (FA)400 mg/m2 on days 1 and 15 and q d29 for 6 cycles fluorouracil (5-FU) 400 mg/m2 bolus + 2400 mg/m2 46-hour infusion on days 1, 2 and 15, 16 and q d29 for 6 cycles or until unacceptable toxicity Cetuximab will be administered as a 120- minute intravenous infusion at 500 mg/m2 on day 1 then 500 mg/m2 bi-weekly

Group Type: EXPERIMENTAL

FOLFIRI + Cetuximab

Intervention Type: DRUG

Interventions

FOLFIRI + Cetuximab

Intervention Type: DRUG

modifiedFOLFOX6 + Cetuximab

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Untreated advanced metastatic colorectal cancer patients
• Adequate tissue to evaluate for genotyping (10 x 10µm thick formalin fixed paraffin embedded tissue sections and one corresponding HE stained slide or a FFPE tumor block)

Patients must fulfill all criteria listed below prior to enrolment in the study:

• Untreated wild-type KRAS metastatic colorectal cancer
• Previous adjuvant therapy must have been completed > 6 months before therapy initiation on this study
• Age >18 years
• Measureable disease with CT or MRI
• ECOG performance status of 0-2
• Adequate organ function

• Hematologic:

• Absolute neutrophil count > 1,500/µL
• Hemoglobin >9 mg/dl
• Platelet count >100,000 /µl
• Renal:

• Serum creatinine <1.5 x Upper limit of normal (UPN) or estimated clearance > 30 ml/min
• Hepatic:

• Serum bilirubin < 1.5 mg/dl

Exclusion Criteria

• Creatinine clearance below 30 ml/min
• Patients with a history of other malignancies within 2 years prior to study entry, except for adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent.
• Patients with a history of severe cardiac disease; e.g. NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, or unstable angina.
• Other known co-morbidity with the potential to dominate survival
• Hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the applied drugs
• Pregnant or breast feeding women
• Any co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Arbeitsgemeinschaft medikamentoese Tumortherapie

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Winder, MD

Role: PRINCIPAL_INVESTIGATOR

LKH Feldkirch, Interne E

Locations

A.ö. Bezirkskrankenhaus Kufstein, Innere Medizin / Hämatologie / Onkologie

Kufstein, Tyrol, Austria

KUK Linz - Med Campus III.: Univ.-Klinik für Hämatologie und Internistische Onkologie

Linz, Upper Austria, Austria

LKH Feldkirch, Interne E

Feldkirch, Vorarlberg, Austria

LKH Bludenz Innere Medizin

Bludenz, , Austria

LKH Bregenz

Bregenz, , Austria

KH Dornbirn, Innere Medizin

Dornbirn, , Austria

Universitätsklinikum Graz

Graz, , Austria

LKH Hohenems, Interne Intensivmedizin

Hohenems, , Austria

Krankenhaus d. Barmherzigen Schwestern Linz

Linz, , Austria

Universitätsklinik für Innere Medizin III mit Hämatologie, internistischer Onkologie, Infektologie, Rheumatologie und Onkologisches Zentrum

Salzburg, , Austria

Medizinische Universität Wien, Univ.Klinik für Innere Medizin I, Abteilung für Onkologie

Vienna, , Austria

Countries

Austria

Other Identifiers

2011-003217-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AGMT_ERCC1

Identifier Type: -

Identifier Source: org_study_id