Clinical trial NCT00003652: Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Stage II or Stage III Anal Cancer
Official title: Intensification Therapy for Locally Advanced Epidermoid Cancer of the Anal Canal - Phase III Intergroup Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anal Cancer
Keywords: stage II anal cancer
stage III anal cancer
squamous cell carcinoma of the anus
cloacogenic carcinoma of the anus
basaloid carcinoma of the anus
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2003-01-27
Enrollment: 350
Sex: ALL
Minimum age (years): 0
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: This randomized phase III trial is studying different regimens of giving combination chemotherapy together with radiation therapy and comparing how well they work in treating patients with stage II or stage III anal cancer.

Detailed description: OBJECTIVES:

* Compare the efficacy of concurrent chemotherapy and radiotherapy with or without neoadjuvant chemotherapy with fluorouracil and cisplatin in patients with stage II or III anal canal cancer.
* Compare the efficacy of two levels of radiation dose in patients with stage II or III anal canal cancer.
* Compare the sphincter conservation of the anus by these regimens.
* Compare the effect of these regimens on survival and quality of life of these patients.

OUTLINE: This is a randomized, multicenter study.

Patients are randomized to one of four treatment arms.

* Arm I: Patients receive induction chemotherapy consisting of fluorouracil IV over 24 hours on days 1-4 and cisplatin IV over 1 hour on day 1 or 2 every 4 weeks for 2 courses. Beginning 4 weeks later, patients receive chemoradiotherapy. This regimen consists of fluorouracil IV over 24 hours on days 1-4 and cisplatin IV over 1 hour on day 1 or 2 and repeated 4 weeks later, plus pelvic radiotherapy beginning on day 1 and continuing for 5 weeks (once a day, 5 days/week). Patients receive low dose radiotherapy directly to the tumor beginning 3 weeks later and continuing for 2 weeks.
* Arm II: Patients receive induction chemotherapy and chemoradiotherapy as in arm I, plus high dose radiotherapy directly to the tumor.
* Arm III (control arm): Patients receive chemoradiotherapy and low dose radiotherapy to the tumor as in arm I.
* Arm IV: Patients receive chemoradiotherapy and high dose radiotherapy to the tumor as in arm II.

After study treatment is completed, patients with nonfixed inguinal tumors may undergo surgical resection followed by radiotherapy or radiotherapy alone. Patients with fixed inguinal tumors may receive further radiotherapy alone.

Quality of life is assessed before treatment, at 2 months after completion of treatment, and at 5 years.

Patients are followed every 4 months for 2 years, every 6 months for 3 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 350 patients will be accrued for this study within 4 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven nonmetastatic anal cancer

  * Anal/rectal junction OR
  * Anal/cutaneous junction with the majority of the tumor in the anal canal, above the junction
  * Epidermoid cancer (well-differentiated, fairly differentiated, or basaloid) OR
  * Cloacogenic cancer
  * Stage II or III

    * T2 at least 4 cm OR
    * T3 OR
    * T4, N0-3, M0 OR
    * T1, N1-3 OR
    * T2 (less than 4 cm), N1-3
* Tumors at least 4 cm in greatest dimension and/or tumors with lymph node invasion must be nonmetastatic by ultrasound
* No prior surgery to remove tumor

PATIENT CHARACTERISTICS:

Age:

* 80 and under

Performance status:

* WHO 0 or 1

Life expectancy:

* Not specified

Hematopoietic:

* WBC at least 2,000/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin at least 11 g/dL (transfusion allowed)

Hepatic:

* Not specified

Renal:

* Creatinine no greater than 1.5 mg/dL

Cardiovascular:

* No cardiac condition contraindicating use of fluorouracil

Other:

* No prior malignancy within 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix or breast
* No other serious medical or psychological condition
* No serious immunosuppression

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior biologic therapy

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* No prior endocrine therapy

Radiotherapy:

* No prior pelvic or inguinal radiotherapy

Surgery:

* See Disease Characteristics
* No prior definitive colostomy

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Angers
country: France
facility: Centre Paul Papin
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Bordeaux
country: France
facility: Institut Bergonie
city: Boulogne Billancourt
country: France
facility: CHU Ambroise Pare
city: Bourg En Bresse
country: France
facility: C.H. Bourg En Bresse
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Chalon Sur Saone
country: France
facility: Centre Hospitalier
city: Colmar
country: France
facility: Hopital Louis Pasteur
city: Creteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Dijon
country: France
facility: Centre de Lutte Contre le Cancer Georges-Francois Leclerc
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: Centre Hospital Regional Universitaire de Limoges
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Institut J. Paoli and I. Calmettes
city: Marseille
country: France
facility: CHU de la Timone
city: Metz
country: France
facility: Hopital Clinique Claude Bernard
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Mulhouse
country: France
facility: Centre Hospitalier de Mulhouse
city: Nancy
country: France
facility: Centre D'Oncologie De Gentilly
city: Nantes-Saint Herblain
country: France
facility: Centre Regional Rene Gauducheau
city: Nante
country: France
facility: Centre Catherine de Sienne
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Orleans
country: France
facility: CHR D'Orleans - Hopital de la Source
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Paris
country: France
facility: Hopital Robert Debre
city: Paris
country: France
facility: Institut Curie - Section Medicale
city: Paris
country: France
facility: Hopital Saint-Louis
city: Paris
country: France
facility: CHU Pitie-Salpetriere
city: Paris
country: France
facility: Hopital Tenon
city: Poitiers
country: France
facility: Hopital Jean Bernard
city: Pontoise
country: France
facility: Clinique Ste - Marie
city: Reims
country: France
facility: Institut Jean Godinot
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Hopital Charles Nicolle
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Brieuc
country: France
facility: Clinique Armoricaine De Radiologie
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Saint Nazaire
country: France
facility: Centre Hospitalier General de Saint Nazaire
city: Strasbourg
country: France
facility: Clinique de l'Orangerie
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Thionville
country: France
facility: Centre Hospitalier Regional Metz Thionville
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Tours
country: France
facility: Clinique Fleming
city: Valence
country: France
facility: Nouvelle Clinique Generale
city: Vandoeuvre-les-Nancy
country: France
facility: Centre Alexis Vautrin
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Alexis Vautrin
name: Didier Peiffert, MD
role: STUDY_CHAIR
References:
citation: Tournier-Rangeard L, Mercier M, Peiffert D, Gerard JP, Romestaing P, Lemanski C, Mirabel X, Pommier P, Denis B. Radiochemotherapy of locally advanced anal canal carcinoma: prospective assessment of early impact on the quality of life (randomized trial ACCORD 03). Radiother Oncol. 2008 Jun;87(3):391-7. doi: 10.1016/j.radonc.2007.12.004. Epub 2008 Jan 11.