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

Anal Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00068744
• Other study ID #: EORTC-22011-40014
• Secondary ID: EORTC-22011EORTC
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: September 10, 2003
• Last updated: September 20, 2012
• Start date: July 2003

Study information

• Verified date: September 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 88
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anal Cancer
• Anus Neoplasms

Intervention

Drug:
• cisplatin

• fluorouracil

• mitomycin C

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Belgium	Ziekenhuis Netwerk Antwerpen Middelheim	Antwerpen
Belgium	Centre Hospitalier Lyon Sud	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Cazk Groeninghe - Campus Maria's Voorzienigheid	Kortrijk
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	Algemeen Ziekenhuis Sint-Augustinus	Wilrijk
Egypt	National Cancer Institute of Egypt	Cairo
France	Institut Sainte Catherine	Avignon
France	Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz	Besancon
France	Centre de Lutte Contre le Cancer Georges-Francois Leclerc	Dijon
Germany	Urologische Klinik - Universitaetsklinikum Aachen	Aachen
Germany	Charite - Campus Charite Mitte	Berlin
Germany	Robert Roessle Comprehensive Cancer Center - Charite Campus Buch	Berlin
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinikum Halle	Halle
Germany	Onkologische Schwerpunktpraxis - Leer	Leer
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Italy	Ospedale Sant Anna	Como
Italy	Ospedale Busonera - Divisione Oncologia Medica	Padova
Netherlands	Arnhems Radiotherapeutisch Instituut	Arnhem
Netherlands	Dr. Bernard Verbeeten Instituut	Tilburg
Serbia	Institute of Oncology and Radiology of Serbia	Belgrade

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  Egypt,  France,  Germany,  Italy,  Netherlands,  Serbia, 

References & Publications (1)

Matzinger O, Roelofsen F, Mineur L, Koswig S, Van Der Steen-Banasik EM, Van Houtte P, Haustermans K, Radosevic-Jelic L, Mueller RP, Maingon P, Collette L, Bosset JF; EORTC Radiation Oncology and Gastrointestinal Tract Cancer Groups. Mitomycin C with conti — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response as measured by RECIST at 8 weeks after completion of study treatment (Phase II)			No
Primary	Event-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III)			No
Secondary	Acute toxicity and compliance to treatment as measured by CTC v 2.0 at completion of study treatment (Phase II)			Yes
Secondary	Colostomy-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III)			No
Secondary	Overall survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter			No
Secondary	Disease-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter			No
Secondary	Local control as measured by Gray at 12 and 26 weeks, then every 6 months thereafter			No
Secondary	Late toxicity as measured by RTOG and EROTC every 6 months after week 26			Yes
Secondary	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			No