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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: Folinic Acid, interferon-alpha


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 5-FU<br>Standard arm Systemic drug administration of 5-FU (intravenous) | Drug: Folinic Acid, interferon-alpha<br>* 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)<br>|
| Experimental: 5-FU + folinic acid<br>Experimental arm Systemic drug administration of 5-FU + folinic acid (intravenous) | Drug: Folinic Acid, interferon-alpha<br>* 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)<br>|
| Experimental: 5-FU + Interferon-alpha<br>Experimental arm Systemic drug administration of 5-FU + interferon-alpha (intravenous) | Drug: Folinic Acid, interferon-alpha<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival |  | 5-year | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rectal cancer, adjuvant chemoradiotherapy, 5-FU, interferon-alpha, Locally advanced resectable rectal cancer (UICC stage II and III)