Clinical trial NCT00025090: Radiation Therapy Plus Fluorouracil With or Without Additional Chemotherapy in Treating Patients With Primary Anal Cancer
Official title: Second UK Phase III Anal Cancer Trial: A Trial of Chemoradiation and Maintenance Therapy for Patients With Anal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anal Cancer
Keywords: stage I anal cancer
stage II anal cancer
stage IIIA anal cancer
stage IIIB anal cancer
squamous cell carcinoma of the anus
cloacogenic carcinoma of the anus
basaloid carcinoma of the anus
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 600
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known if fluorouracil plus radiation therapy is more effective with or without additional chemotherapy in treating anal cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil plus radiation therapy with or without additional chemotherapy in treating patients who have primary anal cancer.

Detailed description: OBJECTIVES:

* Compare the response rates in patients with primary epidermoid anal cancer treated with radiotherapy and fluorouracil with either mitomycin or cisplatin and with or without maintenance therapy.
* Compare local control and prevention or delay of disease dissemination in patients treated with these regimens.

OUTLINE: This is randomized, open-label, multicenter study. Patients are randomized to one of four treatment arms.

All patients undergo radiotherapy daily 5 days a week for 5.5 weeks. All patients also receive fluorouracil IV continuously over days 1-4 and 29-32.

* Arm I: Patients receive mitomycin IV on day 1.
* Arm II: Patients receive cisplatin IV on days 1 and 29.
* Arm III: Patients receive mitomycin as in arm I and maintenance therapy comprising fluorouracil IV continuously over days 1-4 and cisplatin IV on day 1 beginning 4-8 weeks after completion of primary therapy and repeating once 3 weeks later.
* Arm IV: Patients receive cisplatin as in arm II and maintenance therapy as in arm III.

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

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 600 patients (150 per treatment arm) will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed primary epidermoid anal cancer

  * Squamous cell
  * Basaloid
  * Cloacogenic
* No adenocarcinoma, malignant melanoma, mucoepidermoid carcinoma, lymphoma, or microinvasive anal intraepithelial neoplasia (without evidence of invasive disease) in the anal canal or margin
* No metastatic disease

PATIENT CHARACTERISTICS:

Age:

* Not specified

Performance status:

* 0-2

Life expectancy:

* Not specified

Hematopoietic:

* WBC greater than 3,000/mm\^3
* Platelet count greater than 100,000/mm\^3
* Hemoglobin greater than 10 g/dL

Hepatic:

* Liver function tests no greater than 2 times normal

Renal:

* Glomerular filtration rate at least 50 mL/min

Cardiovascular:

* No cardiovascular disease
* No uncontrolled angina pectoris
* No heart failure
* No clinically significant cardiac arrhythmias

Other:

* HIV negative
* No other significant concurrent illness
* Not predominately bed-bound or frail
* No severe sepsis
* No other prior or concurrent cancer or illness that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* Not specified

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy to pelvis

Surgery:

* Not specified

Other:

* No prior therapy for anal cancer

Primary outcomes:
measure: Complete response rate at 6 months
measure: Acute toxicity as measured up to 4 weeks after chemoradiation
measure: Recurrence-free survival
Secondary outcomes:
measure: Colostomy rate
measure: In field recurrence rate as measured by confirmed disease within radiation therapy field
measure: Cause-specific and overall survival
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Leeds
country: United Kingdom
facility: Cookridge Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Cancer Research UK and University College London Cancer Trials Centre
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
Study officials:
affiliation: Maidstone Hospital
name: Roger D. James, MD
role: STUDY_CHAIR
References: