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

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

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.

Study Overview

• Status: Completed
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: Folinic Acid, interferon-alpha

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 Type: Interventional
• Enrollment (Actual): 796
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Ulm, Germany, 89075
    • Department of General, Visceral, and Transplantation Surgery, University of Ulm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall survival	5-year

Secondary Outcome Measures

Outcome Measure	Time Frame
recurrence-free survival	5-year
Toxicity (WHO)	5-year

Collaborators and Investigators

• Sponsor: University of Ulm
• Collaborators: Medac GmbH (Hamburg, Germany); Roche (Grenzach-Wyhlen, Germany)

Study record dates

Study Major Dates

• Study Start: July 1, 1992
• Primary Completion (ACTUAL): July 1, 2009
• Study Completion (ACTUAL): July 1, 2009

Study Registration Dates

• First Submitted: February 1, 2010
• First Submitted That Met QC Criteria: February 1, 2010
• First Posted (ESTIMATE): February 2, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): February 2, 2010
• Last Update Submitted That Met QC Criteria: February 1, 2010
• Last Verified: July 1, 1991

More Information

Terms related to this study

• Keywords: rectal cancer; adjuvant chemoradiotherapy; 5-FU, interferon-alpha; Locally advanced resectable rectal cancer (UICC stage II and III)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Hematinics; Interferons; Interferon-alpha; Leucovorin; Levoleucovorin; Folic Acid
• Other Study ID Numbers: FOGT1