Radiation Therapy, Mitomycin, and Either Fluorouracil or Cisplatin in Treating Patients With Locally Advanced Anal Cancer

Continuous Fluorouracil Plus Mitomycin C Versus Mitomycin C Plus Cisplatin As Chemotherapy Combination In Combined Radiochemotherapy For Locally Advanced Anal Cancer. A Phase II-III Study

RATIONALE: Drugs used in chemotherapy, such as mitomycin, fluorouracil, and cisplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known whether radiation therapy and mitomycin are more effective when combined with fluorouracil or with cisplatin in treating anal cancer .

PURPOSE: This randomized phase II/III trial is studying how well giving radiation therapy and mitomycin together with fluorouracil works compared to radiation therapy, mitomycin, and cisplatin in treating patients with locally advanced anal cancer.

Study Overview

Detailed Description

OBJECTIVES:

Phase II

  • Primary

    • Compare the early clinical response (tumor response at 8 weeks) of patients with locally advanced anal cancer treated with radiotherapy with mitomycin and cisplatin vs mitomycin and fluorouracil.
  • Secondary

    • Compare the feasibility of these regimens in these patients.
    • Compare the acute toxicity of these regimens in these patients.
    • Compare patient compliance to these regimens.

Phase III

  • Primary

    • Compare the event-free survival of patients treated with these regimens.
  • Secondary

    • Compare colostomy-free, disease-free, and overall survival of patients treated with these regimens.
    • Compare locoregional control in patients treated with these regimens.
    • Compare the late toxicity of these regimens in these patients.
    • Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, T stage (T2 vs T3 vs T4), and nodal status (N0 vs N+). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo radiotherapy once daily 5 days a week on weeks 1-4, 7-8, and 3 days of week 9 (total of 33 fractions). Patients concurrently receive fluorouracil IV continuously on days 1-26 and 43-59 and mitomycin IV over 15 minutes on days 1 and 43.
  • Arm II: Patients receive radiotherapy and mitomycin as in arm I and cisplatin IV over 1 hour on days 1, 8, 15, 22, 43, 50, and 57.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, at weeks 12 and 26, and then every 6 months for 2 years.

Patients are followed every 2 weeks for 8 weeks, at week 26, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 678 patients (80 [40 per treatment arm] for phase II and 598 [299 per treatment arm] for phase III) will be accrued for this study within 2-5 years.

Study Type

Interventional

Enrollment (Actual)

88

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Antwerpen, Belgium, B-2020
        • Ziekenhuis Netwerk Antwerpen Middelheim
      • Brussels, Belgium, 1200
        • Cliniques Universitaires Saint-Luc
      • Brussels, Belgium, 1000
        • Institut Jules Bordet
      • Brussels, Belgium, 1200
        • Centre Hospitalier Lyon Sud
      • Edegem, Belgium, B-2650
        • Universitair Ziekenhuis Antwerpen
      • Kortrijk, Belgium, B-8500
        • Cazk Groeninghe - Campus Maria's Voorzienigheid
      • Leuven, Belgium, B-3000
        • U.Z. Gasthuisberg
      • Wilrijk, Belgium, 2610
        • Algemeen Ziekenhuis Sint-Augustinus
      • Cairo, Egypt
        • National Cancer Institute of Egypt
      • Avignon, France, 84082
        • Institut Sainte Catherine
      • Besancon, France, 25030
        • Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
      • Dijon, France, 21079
        • Centre de Lutte Contre le Cancer Georges-Francois Leclerc
      • Aachen, Germany, D-52074
        • Urologische Klinik - Universitaetsklinikum Aachen
      • Berlin, Germany, D-10117
        • Charité - Campus Charité Mitte
      • Berlin, Germany, D-13122
        • Robert Roessle Comprehensive Cancer Center - Charite Campus Buch
      • Essen, Germany, D-45122
        • Universitaetsklinikum Essen
      • Halle, Germany, D-06097
        • Universitaetsklinikum Halle
      • Leer, Germany, D-26789
        • Onkologische Schwerpunktpraxis - Leer
      • Tuebingen, Germany, D-72076
        • Universitaetsklinikum Tuebingen
      • Como, Italy, 22100
        • Ospedale Sant Anna
      • Padova, Italy, 35128
        • Ospedale Busonera - Divisione Oncologia Medica
      • Arnhem, Netherlands, 6815 AD
        • Arnhems Radiotherapeutisch Instituut
      • Tilburg, Netherlands, 5042 SB
        • Dr. Bernard Verbeeten Instituut
      • Belgrade, Serbia, 11000
        • Institute of Oncology and Radiology of Serbia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed squamous cell anal carcinoma

    • Keratinizing or non-keratinizing
    • The following stages are eligible:

      • T2, N0, M0 with maximum tumor diameter at least 4 cm
      • T3-T4, N0, M0
      • Any T, N1-N3, M0
  • Tumor located in the anal canal OR in the anal margin and infiltrating the anal canal
  • No primary adenocarcinoma of the anus
  • Measurable disease

PATIENT CHARACTERISTICS:

Age

  • 18 to 75

Performance status

  • WHO 0-1

Life expectancy

  • Not specified

Hematopoietic

  • Granulocyte count greater than 2,000/mm^3
  • Platelet count greater than 100,000/mm^3

Hepatic

  • Not specified

Renal

  • Creatinine less than 1.4 mg/dL

Cardiovascular

  • No grade I angina pectoris with clinical symptoms within the past 3 months
  • No grade II-IV angina pectoris within the past 3 months
  • No stage II or greater distal arteritis

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No other prior malignancy except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
  • No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No other concurrent chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No other concurrent radiotherapy

Surgery

  • No prior colostomy

Other

  • No prior treatment for anal cancer

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response as measured by RECIST at 8 weeks after completion of study treatment (Phase II)
Event-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III)

Secondary Outcome Measures

Outcome Measure
Acute toxicity and compliance to treatment as measured by CTC v 2.0 at completion of study treatment (Phase II)
Colostomy-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III)
Overall survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter
Disease-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter
Local control as measured by Gray at 12 and 26 weeks, then every 6 months thereafter
Late toxicity as measured by RTOG and EROTC every 6 months after week 26
Quality of life as measured by EORTC Quality of Life Questionnaire-C30 and ASCT at 12 and 26 weeks, then every 6 months for 2 years after entry

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Jean-Francois Bosset, MD, Hopital Jean Minjoz

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2003

Primary Completion (Actual)

November 1, 2007

Study Registration Dates

First Submitted

September 10, 2003

First Submitted That Met QC Criteria

September 10, 2003

First Posted (Estimate)

September 11, 2003

Study Record Updates

Last Update Posted (Estimate)

September 24, 2012

Last Update Submitted That Met QC Criteria

September 20, 2012

Last Verified

September 1, 2012

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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