NCT01703390

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
47

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Dec 2012

Longer than P75 for phase_2

Geographic Reach
1 country

11 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 4, 2012

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 10, 2012

Completed
2 months until next milestone

Study Start

First participant enrolled

December 4, 2012

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 23, 2018

Completed
2.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 3, 2020

Completed
Last Updated

December 21, 2020

Status Verified

December 1, 2020

Enrollment Period

5.2 years

First QC Date

October 4, 2012

Last Update Submit

December 18, 2020

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancermCRCERCC-1ERCC1AGMT

Outcome Measures

Primary Outcomes (1)

  • Response

    Treatment response according to Response Evaluation Criteria In Solid Tumors \[RECIST\]

    5 years

Secondary Outcomes (6)

  • Progression free survival (PFS)

    5 years

  • Response rate

    5 years

  • Patient characteristics

    5 years

  • Secondary resection rate

    5 years

  • Molecular markers for toxicity

    5 years

  • +1 more secondary outcomes

Study Arms (2)

ERCC-1 low

EXPERIMENTAL

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

ERCC-1 high

EXPERIMENTAL

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

Interventions

FOLFIRI + CetuximabDRUG
ERCC-1 high
modifiedFOLFOX6 + CetuximabDRUG
ERCC-1 low

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +2 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

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

Kufstein, Tyrol, 6330, Austria

Location

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

Linz, Upper Austria, 4021, Austria

Location

LKH Feldkirch, Interne E

Feldkirch, Vorarlberg, 6807, Austria

Location

LKH Bludenz Innere Medizin

Bludenz, 6700, Austria

Location

LKH Bregenz

Bregenz, 6900, Austria

Location

KH Dornbirn, Innere Medizin

Dornbirn, 6850, Austria

Location

Universitätsklinikum Graz

Graz, 8036, Austria

Location

LKH Hohenems, Interne Intensivmedizin

Hohenems, 6845, Austria

Location

Krankenhaus d. Barmherzigen Schwestern Linz

Linz, A-4010, Austria

Location

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

Salzburg, 5020, Austria

Location

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

Vienna, 1090, Austria

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Thomas Winder, MD

    LKH Feldkirch, Interne E

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 4, 2012

First Posted

October 10, 2012

Study Start

December 4, 2012

Primary Completion

February 23, 2018

Study Completion

July 3, 2020

Last Updated

December 21, 2020

Record last verified: 2020-12

Locations

AU(11)