Clinical trial NCT01703390: Biomarker Directed Treatment in Metastatic Colorectal Cancer
Official title: Pilot Study: Biomarker Directed Treatment in Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Keywords: metastatic colorectal cancer
mCRC
ERCC-1
ERCC1
AGMT
Lead sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2012-10-10
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Response
timeFrame: 5 years
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: 5 years
measure: Response rate
timeFrame: 5 years
measure: Patient characteristics
timeFrame: 5 years
measure: Secondary resection rate
timeFrame: 5 years
measure: Molecular markers for toxicity
timeFrame: 5 years
measure: Number of adverse events during study treatment
timeFrame: 5 years
Other outcomes:
Locations:
city: Linz
country: Austria
facility: KUK Linz - Med Campus III.: Univ.-Klinik für Hämatologie und Internistische Onkologie
state: Oberösterreich
city: Kufstein
country: Austria
facility: A.ö. Bezirkskrankenhaus Kufstein, Innere Medizin / Hämatologie / Onkologie
state: Tirol
city: Feldkirch
country: Austria
facility: LKH Feldkirch, Interne E
state: Vorarlberg
city: Bludenz
country: Austria
facility: LKH Bludenz Innere Medizin
city: Bregenz
country: Austria
facility: LKH Bregenz
city: Dornbirn
country: Austria
facility: KH Dornbirn, Innere Medizin
city: Graz
country: Austria
facility: Universitätsklinikum Graz
city: Hohenems
country: Austria
facility: LKH Hohenems, Interne Intensivmedizin
city: Linz
country: Austria
facility: Krankenhaus d. Barmherzigen Schwestern Linz
city: Salzburg
country: Austria
facility: Universitätsklinik für Innere Medizin III mit Hämatologie, internistischer Onkologie, Infektologie, Rheumatologie und Onkologisches Zentrum
city: Vienna
country: Austria
facility: Medizinische Universität Wien, Univ.Klinik für Innere Medizin I, Abteilung für Onkologie
Study officials:
affiliation: LKH Feldkirch, Interne E
name: Thomas Winder, MD
role: PRINCIPAL_INVESTIGATOR
References: