FOGT1: Modulation of Adjuvant 5-FU by Folinic Acid and Interferon-alpha in Colon Cancer

Sponsor

University of Ulm (Other)

Overall Status

Completed

CT.gov ID

NCT01060501

Collaborator

Medac GmbH (Hamburg, Germany) (Other), Roche (Grenzach-Wyhlen, Germany) (Other)

796

Enrollment

Location

Arms

204

Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective was to improve adjuvant 5-FU chemoradiotherapy in resectable rectal cancer. The investigators hypothesis was that modulation of 5-FU by addition of either FA or INF-alpha may increase overall survival.

Condition or Disease	Intervention/Treatment	Phase
Rectal Cancer	Drug: Folinic Acid, interferon-alpha	Phase 3

Detailed Description

Primary endpoint was overall survival (OS). For sample size estimation the following assumptions were made: The 5-year OS rate of 5-FU was estimated to be 58%. Our intention was to detect an increase in the 5-year OS rate by one of the additives of at least 10% with a power of 80% and a level of significance of 5% in comparison to 5-FU (one-sided). Hypotheses were analyzed as pair wise comparisons between the treatment options. This resulted in a target sample size of 280 patients per group and a total of 840 patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

796 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase 3 Study of Adjuvant Chemoradiotherapy of Advanced Resectable Rectal Cancer Comparing Modulation of 5-FU With Folinic Acid or With Interferon-alpha

Study Start Date :

Jul 1, 1992

Actual Primary Completion Date :

Jul 1, 2009

Actual Study Completion Date :

Jul 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 5-FU Standard arm Systemic drug administration of 5-FU (intravenous)	Drug: Folinic Acid, interferon-alpha 5-FU, 450 mg/m² i.v. for 60 min, weekly for 52 weeks postoperatively Folinic acid, 200 mg/m² i.v. 10 min, weekly for 52 weeks postoperatively 6x10 (high6) I.U. as subcutaneous self injection 3x weekly. Training of self injection was initiated on day 28 (duration until week 52)
Experimental: 5-FU + folinic acid Experimental arm Systemic drug administration of 5-FU + folinic acid (intravenous)	Drug: Folinic Acid, interferon-alpha 5-FU, 450 mg/m² i.v. for 60 min, weekly for 52 weeks postoperatively Folinic acid, 200 mg/m² i.v. 10 min, weekly for 52 weeks postoperatively 6x10 (high6) I.U. as subcutaneous self injection 3x weekly. Training of self injection was initiated on day 28 (duration until week 52)
Experimental: 5-FU + Interferon-alpha Experimental arm Systemic drug administration of 5-FU + interferon-alpha (intravenous)	Drug: Folinic Acid, interferon-alpha 5-FU, 450 mg/m² i.v. for 60 min, weekly for 52 weeks postoperatively Folinic acid, 200 mg/m² i.v. 10 min, weekly for 52 weeks postoperatively 6x10 (high6) I.U. as subcutaneous self injection 3x weekly. Training of self injection was initiated on day 28 (duration until week 52)

Arm

Intervention/Treatment

Active Comparator: 5-FU

Standard arm Systemic drug administration of 5-FU (intravenous)

Drug: Folinic Acid, interferon-alpha

5-FU, 450 mg/m² i.v. for 60 min, weekly for 52 weeks postoperatively Folinic acid, 200 mg/m² i.v. 10 min, weekly for 52 weeks postoperatively 6x10 (high6) I.U. as subcutaneous self injection 3x weekly. Training of self injection was initiated on day 28 (duration until week 52)

Experimental: 5-FU + folinic acid

Experimental arm Systemic drug administration of 5-FU + folinic acid (intravenous)

Drug: Folinic Acid, interferon-alpha

Experimental: 5-FU + Interferon-alpha

Experimental arm Systemic drug administration of 5-FU + interferon-alpha (intravenous)

Drug: Folinic Acid, interferon-alpha

Outcome Measures

Primary Outcome Measures

overall survival [5-year]

Secondary Outcome Measures

recurrence-free survival [5-year]
Toxicity (WHO) [5-year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Eligibility was defined as potentially curative en-bloc resection (R0) of an adenocarcinoma of the rectum with a lower tumor edge within 12 cm from the anal verge determined by rectoscopy, a pathologic UICC stage II (pT3/4pN0M0) or III (pT1-4pNposM0) with examination of at least 12 lymph nodes, a white blood count ≥ 3,500/µl, a platelet count ≥ 100,000/µl, a ECOG performance status of 0 or 1, and written informed consent.

Exclusion Criteria:

Ineligible were patients not fulfilling these criteria or having a history of cancer except for adequately treated superficial basal or squamous cell skin cancer or in situ carcinoma of the cervix, getting previous radio- or chemotherapy, pregnant or nursing women, other having severe concomitant diseases limiting life expectancy or not allowing chemotherapy, and with social conditions not allowing a 5-year follow-up.