This trial is active, not recruiting.

Condition anal cancer
Treatments fluorouracil, mitomycin c, intensity-modulated radiation therapy
Phase phase 2
Sponsor Radiation Therapy Oncology Group
Collaborator National Cancer Institute (NCI)
Start date December 2006
End date February 2009
Trial size 63 participants
Trial identifier NCT00423293, CDR0000524057, RTOG-0529


RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as fluorouracil and mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy together with 5-fluorouracil (5-FU) and mitomycin C may kill more tumor cells.

PURPOSE: This phase II trial is studying the side effects and how well giving intensity-modulated radiation therapy together with fluorouracil and mitomycin C works in treating patients with invasive anal cancer.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Intervention model single group assignment
Masking open label
Primary purpose treatment
5-FU + Mitomycin + IMRT
1000 mg/m^2/day 96-hour continous infusion (M-F) starting on day 1 and again on day 29 of radiation therapy.
mitomycin c
10 mg/m^2 intravenous therapy on day 1 and day 29 of radiation therapy.
intensity-modulated radiation therapy
Prescription dose depends on tumor staging. T2N0: The primary tumor PTV (planning target volume) (PTVA) receives 50.4 Gy in 28 fractions (fx) at 1.8 Gy/fx. The nodal PTVs receive 42 Gy in 28 fx at 1.5 Gy/fx. PTVA receive 50.4 Gy in 28 fractions at 1.8 Gy/fx. PTV42 receive 42 Gy in 28 fx at 1.5 Gy/fx and will include all nodal regions. T3N0 or T4N0: The primary tumor PTV (PTVA) will receive 54 Gy in 30 fx at 1.8 Gy/fx. The nodal PTVs will receive 45 Gy in 30 fx at 1.5 Gy/fx. PTVA will receive 54 Gy in 30 fx at 1.80 Gy/fx. PTV45 will receive 45 Gy in 30 fx electively at 1.5 Gy/fx and will include all nodal regions. For N+ disease: The primary tumor PTV (PTVA) will receive 54 Gy in 30 fx at 1.8 Gy/fx. For involved nodes ≤ 3 cm in maximum dimension, the involved nodal PTV will receive 50.4 Gy in 30 fx at 1.68 Gy/fx. For involved nodes > 3 cm in maximum dimension, the involved nodal PTV will receive 54 Gy in 30 fx at 1.80 Gy/fx.

Primary Outcomes

Gastrointestinal (GI) and Genitourinary (GU) Adverse Events (AE) ≥ Grade 2 as Defined by CTCAE v3.0 (Common Terminology Criteria for Adverse Events)
time frame: From the start of treatment to 90 days

Secondary Outcomes

Reproducibility of the Intensity-modulated Radiation Therapy Technique
time frame: IMRT planning and dosing data is centrally reviewed for quality assurance
Adverse Event Rates as Defined by CTCAE v 3.0 Within 90 Days From the Start of Study Treatment
time frame: From the start of treatment to 90 days
Clinical Complete Response Rate
time frame: From registration to 8 and 12 weeks after treatment completion
Radiotherapy Treatment Time
time frame: From start to end of radiation therapy
Efficacy of Treatment, in Terms of Locoregional Failure, Disease-free Survival, Time to Colostomy, Colostomy-free Survival, and Overall Survival
time frame: From registration to date of failure, death or last follow-up. Analysis occurs after all patients have been potentially followed for 2 years.

Eligibility Criteria

Male or female participants at least 18 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed carcinoma of the anal canal, including any of the following subtypes: - Squamous cell - Basaloid - Cloacogenic - Primary invasive disease - T2-4, N0-3 disease - Clinically positive small inguinal nodes (i.e., < 1 cm in size) must be confirmed by biopsy (preferably fine-needle aspiration) within the past 6 weeks - Biopsy is not required for enlarged inguinal, perirectal, or pelvic nodes on exam or CT scan that are found to be ≥ 1.0 cm and are considered to be clinically positive PATIENT CHARACTERISTICS: - Zubrod performance status 0-1 - Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention allowed) - ALT and AST < 3 times upper limit of normal - Absolute neutrophil count ≥ 1,800/mm³ - Serum creatinine ≤ 1.5 mg/dL - Platelet count ≥ 100,000/mm³ - Bilirubin < 1.4 mg/dL - WBC ≥ 3,000/mm³ - INR ≤ 1.5 - No known AIDS - HIV-positive patients without AIDS are eligible - HIV test required for patients with clinical suspicion of AIDS - No other invasive malignancy within the past 3 years except for nonmelanomatous skin cancer - No severe, active comorbidity, defined as any of the following: - Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months - Transmural myocardial infarction within the past 6 months - Acute bacterial or fungal infection requiring IV antibiotics - Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study treatment - Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects - Uncontrolled diabetes mellitus, uncompensated heart disease, and/or uncontrolled high blood pressure, that in the opinion of the patient's treating physician, requires an immediate change in management - Patients may be eligible if appropriate changes in management have resulted in adequate control of the above mentioned conditions - Other immunocompromised status (e.g., organ transplantation or chronic glucocorticoid use) - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: - See Disease Characteristics - No prior radiation therapy to the pelvis that would result in overlap of radiation therapy fields - No prior systemic chemotherapy for cancer of the anus - No prior surgery for cancer of the anus that removed all macroscopic anal cancer - No concurrent sargramostim (GM-CSF) - No concurrent amifostine

Additional Information

Official title A Phase II Evaluation of Dose-Painted Intensity-Modulated Radiation Therapy (IMRT) in Combination With 5-Fluorouracil (5-FU) and Mitomycin-C for Reduction of Acute Morbidity in Carcinoma of the Anal Canal
Description OBJECTIVES: Primary - Determine if dose-painted, intensity-modulated radiation therapy (IMRT), fluorouracil, and mitomycin C decreases the combined rate of gastrointestinal and genitourinary adverse events (grade II or greater) by at least 15% in the first 90 days after the start of treatment in patients with primary invasive carcinoma of the anal canal compared to patients treated on the radiotherapy, fluorouracil, and mitomycin C arm on clinical trial RTOG 98-11. Secondary - Determine the feasibility of performing IMRT in these patients in a cooperative group setting. - Evaluate adverse events experienced by patients treated with this regimen and to decrease the grade 2 and higher and grade 3 and higher overall adverse event rates by 15% or 20% as compared to the radiotherapy and mitomycin C arm of RTOG 98-11. - Evaluate the total duration of radiotherapy. - Evaluate the efficacy of this regimen, in terms of locoregional failure, disease-free survival, time to colostomy, colostomy-free survival, and overall survival of these patients. - Determine clinical complete response at 8 weeks after completion of study treatment. OUTLINE: This is a multicenter study. Patients receive mitomycin C IV over 10-30 minutes on days 1 and 29 and fluorouracil IV continuously over 96 hours on days 1-4 and 29-32. Patients also undergo dose-painted intensity-modulated radiation therapy once daily, 5 days a week, for 5½ to 6 weeks beginning on day 1. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: A total of 59 patients will be accrued for this study.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Radiation Therapy Oncology Group.