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

This study has been terminated.
(low accrual)
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00068744
First received: September 10, 2003
Last updated: September 20, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Anal Cancer
Drug: cisplatin
Drug: fluorouracil
Drug: mitomycin C
Radiation: radiation therapy
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Response as measured by RECIST at 8 weeks after completion of study treatment (Phase II) [ Designated as safety issue: No ]
  • Event-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Acute toxicity and compliance to treatment as measured by CTC v 2.0 at completion of study treatment (Phase II) [ Designated as safety issue: Yes ]
  • Colostomy-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III) [ Designated as safety issue: No ]
  • Overall survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter [ Designated as safety issue: No ]
  • Disease-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter [ Designated as safety issue: No ]
  • Local control as measured by Gray at 12 and 26 weeks, then every 6 months thereafter [ Designated as safety issue: No ]
  • Late toxicity as measured by RTOG and EROTC every 6 months after week 26 [ Designated as safety issue: Yes ]
  • 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 [ Designated as safety issue: No ]

Enrollment: 88
Study Start Date: July 2003
Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00068744

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

Publications:
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00068744     History of Changes
Other Study ID Numbers: EORTC-22011-40014, EORTC-22011, EORTC-40014
Study First Received: September 10, 2003
Last Updated: September 20, 2012
Health Authority: United States: Federal Government

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
squamous cell carcinoma of the anus
stage II anal cancer
stage IIIA anal cancer
stage IIIB anal cancer

Additional relevant MeSH terms:
Anus Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Mitomycins
Mitomycin
Cisplatin
Fluorouracil
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Radiation-Sensitizing Agents
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 21, 2014