Biomarker Directed Treatment in Metastatic Colorectal Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Arbeitsgemeinschaft medikamentoese Tumortherapie
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Arbeitsgemeinschaft medikamentoese Tumortherapie
ClinicalTrials.gov Identifier:
NCT01703390
First received: October 4, 2012
Last updated: October 8, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: FOLFIRI + Cetuximab
Drug: modifiedFOLFOX6 + Cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:

Primary Outcome Measures:
  • Response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Treatment response according to Response Evaluation Criteria In Solid Tumors [RECIST]


Secondary Outcome Measures:
  • Feasibility [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To establish the feasibility of conducting a biomarker based trial of ERCC-1, in wt KRAS mCRC patients in the cooperative group setting to assess progression free survival (PFS) and overall survival (OS) intients with biomarker directed treatment

  • Response rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to response rate, PFS and OS

  • Patient characteristics [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to KRAS status

  • Secondary resection rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Molecular markers for toxicity [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Analysis of occuring adverse events during the study treatment according to Common Terminology Criteria for Adverse Events (CTCAE)


Estimated Enrollment: 30
Study Start Date: August 2012
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Drug: modifiedFOLFOX6 + Cetuximab
Experimental: 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
Drug: FOLFIRI + Cetuximab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01703390

Contacts
Contact: Richard Greil, MD 00436628842 ext 4109 d.wolkersdorfer@agmt.at

Locations
Austria
AKH Linz, Innere Medizin 3, Zentrum für Hämatologie und medizinische Onkologie Recruiting
Linz, Oberösterreich, Austria, 4021
Principal Investigator: Michael Fridrik, MD         
A.ö. Bezirkskrankenhaus Kufstein, Innere Medizin / Hämatologie / Onkologie Not yet recruiting
Kufstein, Tirol, Austria, 6330
Contact: August Zabernigg, OA Dr.       august.zabernigg@bkh-kufstein.at   
Principal Investigator: August Zabernigg, OA Dr.         
LKH Feldkirch, Interne E Recruiting
Feldkirch, Vorarlberg, Austria, 6807
Contact: Alois Lang, Dr.       alois.lang@lkhf.at   
Principal Investigator: Alois Lang, OA Dr.         
LKH Bludenz Innere Medizin Not yet recruiting
Bludenz, Austria, 6700
Principal Investigator: Othmar Thurnes, MD         
LKH Bregenz Recruiting
Bregenz, Austria, 6900
Principal Investigator: Franz X Schmid, Dr         
KH Dornbirn, Innere Medizin Not yet recruiting
Dornbirn, Austria, 6850
Principal Investigator: Guntram Winder, MD         
Universitätsklinikum Graz Recruiting
Graz, Austria, 8036
Principal Investigator: Helmuth Samonigg, MD         
LKH Hohenems, Interne Intensivmedizin Not yet recruiting
Hohenems, Austria, 6845
Principal Investigator: Günter Höfle, MD         
Krankenhaus d. Barmherzigen Schwestern Linz Not yet recruiting
Linz, Austria, A-4010
Principal Investigator: Andreas Petzer, MD         
Universitätsklinik für Innere Medizin III mit Hämatologie, internistischer Onkologie, Infektologie, Rheumatologie und Onkologisches Zentrum Recruiting
Salzburg, Austria, 5020
Contact: Richard Greil, Prof. Dr.    0043/662/4482 ext 2879    r.greil@salk.at   
Principal Investigator: Richard Greil, MD         
Sponsors and Collaborators
Arbeitsgemeinschaft medikamentoese Tumortherapie
Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Arbeitsgemeinschaft medikamentoese Tumortherapie
ClinicalTrials.gov Identifier: NCT01703390     History of Changes
Other Study ID Numbers: AGMT_ERCC1, 2011-003217-41
Study First Received: October 4, 2012
Last Updated: October 8, 2012
Health Authority: Austria: Agency for Health and Food Safety

Keywords provided by Arbeitsgemeinschaft medikamentoese Tumortherapie:
metastatic colorectal cancer
mCRC
ERCC-1
ERCC1
AGMT

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014