Back to results

Biomarker Directed Treatment in Metastatic Colorectal Cancer

Primary Purpose

Metastatic Colorectal Cancer

Status

Completed

Phase

Phase 2

Locations

Austria

Study Type

Interventional

Intervention

FOLFIRI + Cetuximab

modifiedFOLFOX6 + Cetuximab

About this trial

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring metastatic colorectal cancer, mCRC, ERCC-1, ERCC1, AGMT

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

KUK Linz - Med Campus III.: Univ.-Klinik für Hämatologie und Internistische Onkologie
A.ö. Bezirkskrankenhaus Kufstein, Innere Medizin / Hämatologie / Onkologie
LKH Feldkirch, Interne E
LKH Bludenz Innere Medizin
LKH Bregenz
KH Dornbirn, Innere Medizin
Universitätsklinikum Graz
LKH Hohenems, Interne Intensivmedizin
Krankenhaus d. Barmherzigen Schwestern Linz
Universitätsklinik für Innere Medizin III mit Hämatologie, internistischer Onkologie, Infektologie, Rheumatologie und Onkologisches Zentrum
Medizinische Universität Wien, Univ.Klinik für Innere Medizin I, Abteilung für Onkologie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

ERCC-1 low

ERCC-1 high

Arm Description

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

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

Outcomes

Primary Outcome Measures

Response

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

Secondary Outcome Measures

Progression free survival (PFS)

Response rate

Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to response rate, PFS and OS

Patient characteristics

Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to KRAS status

Secondary resection rate

Molecular markers for toxicity

Number of adverse events during study treatment

Full Information

NCT ID

NCT01703390

First Posted

October 4, 2012

Last Updated

December 18, 2020

Sponsor

Arbeitsgemeinschaft medikamentoese Tumortherapie

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01703390

Brief Title

Biomarker Directed Treatment in Metastatic Colorectal Cancer

Official Title

Pilot Study: Biomarker Directed Treatment in Metastatic Colorectal Cancer

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

December 4, 2012 (Actual)

Primary Completion Date

February 23, 2018 (Actual)

Study Completion Date

July 3, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Arbeitsgemeinschaft medikamentoese Tumortherapie

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Colorectal Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

47 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ERCC-1 low

Arm Type

Experimental

Arm Description

Arm Title

ERCC-1 high

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

FOLFIRI + Cetuximab

Intervention Type

Drug

Intervention Name(s)

modifiedFOLFOX6 + Cetuximab

Primary Outcome Measure Information:

Title

Response

Description

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

Time Frame

5 years

Secondary Outcome Measure Information:

Title

Progression free survival (PFS)

Time Frame

5 years

Title

Response rate

Description

Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to response rate, PFS and OS

Time Frame

5 years

Title

Patient characteristics

Description

Description of group differences between ERCC-1 low and ERCC-1 high patients with respect to KRAS status

Time Frame

5 years

Title

Secondary resection rate

Time Frame

5 years

Title

Molecular markers for toxicity

Time Frame

5 years

Title

Number of adverse events during study treatment

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Thomas Winder, MD

Organizational Affiliation

LKH Feldkirch, Interne E

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Linz

State/Province

Oberösterreich

ZIP/Postal Code

4021

Country

Austria

Facility Name

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

City

Kufstein

State/Province

Tirol

ZIP/Postal Code

6330

Country

Austria

Facility Name

LKH Feldkirch, Interne E

City

Feldkirch

State/Province

Vorarlberg

ZIP/Postal Code

6807

Country

Austria

Facility Name

LKH Bludenz Innere Medizin

City

Bludenz

ZIP/Postal Code

6700

Country

Austria

Facility Name

LKH Bregenz

City

Bregenz

ZIP/Postal Code

6900

Country

Austria

Facility Name

KH Dornbirn, Innere Medizin

City

Dornbirn

ZIP/Postal Code

6850

Country

Austria

Facility Name

Universitätsklinikum Graz

City

Graz

ZIP/Postal Code

8036

Country

Austria

Facility Name

LKH Hohenems, Interne Intensivmedizin

City

Hohenems

ZIP/Postal Code

6845

Country

Austria

Facility Name

Krankenhaus d. Barmherzigen Schwestern Linz

City

Linz

ZIP/Postal Code

A-4010

Country

Austria

Facility Name

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

City

Salzburg

ZIP/Postal Code

5020

Country

Austria

Facility Name

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

City

Vienna

ZIP/Postal Code

1090

Country

Austria

12. IPD Sharing Statement

Learn more about this trial

Biomarker Directed Treatment in Metastatic Colorectal Cancer

We'll reach out to this number within 24 hrs