Intensity-Modulated Radiation Therapy, Fluorouracil, and Mitomycin C in Treating Patients With Invasive Anal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00423293
First received: January 16, 2007
Last updated: June 26, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Anal Cancer
Drug: fluorouracil
Drug: mitomycin C
Radiation: Intensity-modulated radiation therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Reproducibility of the Intensity-modulated Radiation Therapy Technique [ Time Frame: IMRT planning and dosing data is centrally reviewed for quality assurance ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Clinical Complete Response Rate [ Time Frame: From registration to 8 and 12 weeks after treatment completion ] [ Designated as safety issue: No ]
  • Radiotherapy Treatment Time [ Time Frame: From start to end of radiation therapy ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: December 2006
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
5-FU + Mitomycin + IMRT
5-FU + Mitomycin + IMRT
Drug: fluorouracil
1000 mg/m^2/day 96-hour continous infusion (M-F) starting on day 1 and again on day 29 of radiation therapy.
Drug: mitomycin C
10 mg/m^2 intravenous therapy on day 1 and day 29 of radiation therapy.
Radiation: 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.


Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00423293

  Show 172 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: Lisa A. Kachnic, MD Boston Medical Center
  More Information

Additional Information:
Publications:
Kachnic LA, Winter KA, Myerson RJ, et al.: RTOG 0529: A phase II study of dose-painted IMRT (DP-IMRT), 5-fluorouracil, and mitomycin-C for the reduction of acute morbidity in anal cancer. [Abstract] American Society of Clinical Oncology 2010 Gastrointestinal Cancers Symposium, 22-24 January 2010, Orlando, Florida. A-405, 2010.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00423293     History of Changes
Other Study ID Numbers: RTOG-0529, CDR0000524057
Study First Received: January 16, 2007
Results First Received: April 11, 2013
Last Updated: June 26, 2013
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
stage II anal cancer
stage IIIA anal cancer
stage IIIB anal cancer
basaloid carcinoma of the anus
cloacogenic carcinoma of the anus
squamous cell carcinoma of the anus

Additional relevant MeSH terms:
Anus Neoplasms
Anus Diseases
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Rectal Neoplasms
Fluorouracil
Mitomycin
Mitomycins
Alkylating Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014