Clinical trial NCT00068744: Radiation Therapy, Mitomycin, and Either Fluorouracil or Cisplatin in Treating Patients With Locally Advanced Anal Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Anal Cancer
Keywords: squamous cell carcinoma of the anus
stage II anal cancer
stage IIIA anal cancer
stage IIIB anal cancer
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-09-11
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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 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

Primary outcomes:
measure: Response as measured by RECIST at 8 weeks after completion of study treatment (Phase II)
measure: Event-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III)
Secondary outcomes:
measure: Acute toxicity and compliance to treatment as measured by CTC v 2.0 at completion of study treatment (Phase II)
measure: Colostomy-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter (Phase III)
measure: Overall survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter
measure: Disease-free survival as measured by Logrank at 12 and 26 weeks, then every 6 months thereafter
measure: Local control as measured by Gray at 12 and 26 weeks, then every 6 months thereafter
measure: Late toxicity as measured by RTOG and EROTC every 6 months after week 26
measure: 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
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Middelheim
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Centre Hospitalier Lyon Sud
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Kortrijk
country: Belgium
facility: Cazk Groeninghe - Campus Maria's Voorzienigheid
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Wilrijk
country: Belgium
facility: Algemeen Ziekenhuis Sint-Augustinus
city: Cairo
country: Egypt
facility: National Cancer Institute of Egypt
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Besancon
country: France
facility: Centre Hospitalier Regional de Besancon - Hopital Jean Minjoz
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: Aachen
country: Germany
facility: Urologische Klinik - Universitaetsklinikum Aachen
city: Berlin
country: Germany
facility: Charite - Campus Charite Mitte
city: Berlin
country: Germany
facility: Robert Roessle Comprehensive Cancer Center - Charite Campus Buch
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Halle
country: Germany
facility: Universitaetsklinikum Halle
city: Leer
country: Germany
facility: Onkologische Schwerpunktpraxis - Leer
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Como
country: Italy
facility: Ospedale Sant Anna
city: Padova
country: Italy
facility: Ospedale Busonera - Divisione Oncologia Medica
city: Arnhem
country: Netherlands
facility: Arnhems Radiotherapeutisch Instituut
city: Tilburg
country: Netherlands
facility: Dr. Bernard Verbeeten Instituut
city: Belgrade
country: Serbia
facility: Institute of Oncology and Radiology of Serbia
Study officials:
affiliation: Hopital Jean Minjoz
name: Jean-Francois Bosset, MD
role: STUDY_CHAIR
References:
citation: 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 continuous fluorouracil or with cisplatin in combination with radiotherapy for locally advanced anal cancer (European Organisation for Research and Treatment of Cancer phase II study 22011-40014). Eur J Cancer. 2009 Nov;45(16):2782-91. doi: 10.1016/j.ejca.2009.06.020. Epub 2009 Jul 28.