Response Prediction in Metastasized Colorectal Cancer Using Intratumoral Thymidylate Synthase (FOGT5)

Stratified and Randomized Multi-center Phase II - to Determine Potential Benefit of Treating Patients With Advanced Colorectal Cancer According to the Intratumoral TS RNA Levels

The aim of the study was to evaluate the feasibility of TS determination in a multicenter trial setting using a central facility for measurement and confirm its role as predictive factor for 5-FU treatment in MCRC.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Biopsy; Non Resectable Metastasis; Reference Lesion; Thymidylate Synthase Quantitation
• Intervention / Treatment: Drug: FUFA; Drug: systemic chemotherapy

Detailed Description

Eligible were patients with non-resectable metastasized or recurrent histologically proven CRC with the presence of a reference lesion two-dimensional measurable and accessible for a biopsy.The biopsy was taken from the reference lesion either by surgery during primary tumor resection, by trans-cutaneous true-cut needle biopsy or by trans-anal approach. Intratumoral relative TS mRNA expression levels were determined using samples shipped in RNA-preserving solution or as glass slides after microdissection of tumor cells. An independent company stratified the patients according to ther relative TS mRNA expression level in TS low and TS high followed by randomization to receive either FUFA of Folfiri. Response to chemotherapy was evaluated and documented according to the RECIST criteria after every therapy cycle.

• Study Type: Interventional
• Enrollment (Actual): 168
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Ulm, Germany
    • Department of General, Visceral, and Transplantations Surgery, Univeristy of Ulm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients (>= 18 years) with non-resectable metastasized or recurrent histologically proven CRC with the presence of a reference lesion two-dimensional measurable and accessible for a biopsy
• a performance status WHO 0-2 (Karnofsky >= 60%)
• an estimated life expectancy of at least 3 months
• written informed consent

Exclusion Criteria:

• patients older than 75 years not fulfilling these criteria
• brain metastases or a secondary cane
• a history of a systemic palliative chemotherapy
• and an adjuvant chemotherapy (within 6 months)
• pregnant or nursing women
• a known allergy toward irinotecanhydroclorid or of any ingredients of Campto or other severe medical
• laboratory and social conditions not allowing chemotherapy and follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 5-FU; FUFA 5-flurouracil and folinic acid control	Drug: FUFA; 2600/500 mg/m2 i.v. 24 h via port, 1 time weekly for six weeks, than have a break for 2 weeks (=8 weeks for 1 cycle)
Active Comparator: Folfiri; 5-fluouracil and folinic acid in combination with irinotecan (Folfiri) systemic chemotherapy intensified treatment arm	Drug: systemic chemotherapy; CPT-11, 80 mg/m2 for 90 minutes and 5 FU/FA 2000/500 mg/m2 iv. 24h via port; 1 time weekly for six weeks, than have a break for 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best response to first-line chemotherapy (recist)	Response to chemotherapy was evaluated and documented according to the RECIST criteria after every therapy cycle (every two months).	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival, toxicity, treatment related complications, time to progression	See above.	3-year

Collaborators and Investigators

• Sponsor: University of Ulm
• Collaborators: Pfizer, Berlin Germany; Medac, Hamburg, Germany; Study Group Oncology of Gastrointestinal Tumors (FOGT)

Study record dates

Study Major Dates

• Study Start: July 1, 2001
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: September 9, 2010
• First Submitted That Met QC Criteria: September 30, 2010
• First Posted (Estimate): October 1, 2010

Study Record Updates

• Last Update Posted (Estimate): October 1, 2010
• Last Update Submitted That Met QC Criteria: September 30, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: Colorectal Cancer; biopsy; non resectable metastasis; reference lesion; thymidylate synthase quantitation
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: FOGT5