Biomarker Directed Treatment in Metastatic Colorectal Cancer

Metastatic Colorectal Cancer Clinical Trial

Official title:

Pilot Study: Biomarker Directed Treatment in Metastatic Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01703390
• Other study ID #: AGMT_ERCC1
• Secondary ID: 2011-003217-41
• Status: Completed
• Phase: Phase 2
• Start date: December 4, 2012
• Est. completion date: July 3, 2020

Study information

• Verified date: December 2020
• Source: Arbeitsgemeinschaft medikamentoese Tumortherapie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: July 3, 2020
• Est. primary completion date: February 23, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1.1 Inclusion criteria for pre-screening phase:

• 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)

1.2 Inclusion criteria for treatment phase:

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• FOLFIRI + Cetuximab

• modifiedFOLFOX6 + Cetuximab

Locations

Country	Name	City	State
Austria	LKH Bludenz Innere Medizin	Bludenz
Austria	LKH Bregenz	Bregenz
Austria	KH Dornbirn, Innere Medizin	Dornbirn
Austria	LKH Feldkirch, Interne E	Feldkirch	Vorarlberg
Austria	Universitätsklinikum Graz	Graz
Austria	LKH Hohenems, Interne Intensivmedizin	Hohenems
Austria	A.ö. Bezirkskrankenhaus Kufstein, Innere Medizin / Hämatologie / Onkologie	Kufstein	Tirol
Austria	Krankenhaus d. Barmherzigen Schwestern Linz	Linz
Austria	KUK Linz - Med Campus III.: Univ.-Klinik für Hämatologie und Internistische Onkologie	Linz	Oberösterreich
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

Sponsors (2)

Lead Sponsor	Collaborator
Arbeitsgemeinschaft medikamentoese Tumortherapie	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response	Treatment response according to Response Evaluation Criteria In Solid Tumors [RECIST]	5 years
Secondary	Progression free survival (PFS)		5 years
Secondary	Response rate	Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to response rate, PFS and OS	5 years
Secondary	Patient characteristics	Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to KRAS status	5 years
Secondary	Secondary resection rate		5 years
Secondary	Molecular markers for toxicity		5 years
Secondary	Number of adverse events during study treatment		5 years