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Topical MTS-01 for Dermatitis During Radiation and Chemotherapy for Anal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01324141
Recruitment Status : Terminated
First Posted : March 28, 2011
Last Update Posted : July 5, 2018
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE March 25, 2011
First Posted Date  ICMJE March 28, 2011
Last Update Posted Date July 5, 2018
Study Start Date  ICMJE March 18, 2011
Actual Primary Completion Date April 15, 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 12, 2014)
To determine the safety and tolerability of topical MTS-01 on a daily basis prior to irradiation in the groin and gluteal cleft of patients receiving combined therapy with MMC, 5-FU, and RT for carcinoma of the anal canal. [ Time Frame: Completion of study ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 25, 2011)
To determine the safety and tolerability of topical MTS-01 on a daily basis prior to irradiation in the groin and gluteal cleft of patients receiving combined therapy with MMC, 5-FU, and RT for carcinoma of the anal canal.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2014)
  • To describe the rates and severity of skin toxicity in patients treated with this regimen [ Time Frame: Completion of study ]
  • To describe the need for toxicity related treatment breaks with this regimen [ Time Frame: Completion of study ]
  • To describe the opiate requirements in patients treated with this regimen [ Time Frame: Completion of study ]
  • To describe 12-month progression-free survival, disease-free survival, and overall survival in patients treated with concurrent chemotherapy, radiation therapy, MTS-01 [ Time Frame: Completion of study ]
  • Evaluate the effects of antiretroviral therapy, 5-fluorouracil, mitomycin C, and radiation on low level persistent HIV viremia and HIV genetic diversity [ Time Frame: Completion of study ]
  • To evaluate the feasibility of collecting HIV RNA and mononuclear cells from rectal associated lymphoid tissue for correlative studies [ Time Frame: Completion of study ]
  • Collect and store anal cytology and core needle biopsies of tumor for future HPV and tumor based analyses [ Time Frame: Completion of study ]
Original Secondary Outcome Measures  ICMJE
 (submitted: March 25, 2011)
Evaluation of the following: rates and severity of skin toxicity, need for toxicity related treatment breaks, opiate requirements, disease status, HIV status, feasibility of collecting HIV RNA, cytology, and HPV studies.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Topical MTS-01 for Dermatitis During Radiation and Chemotherapy for Anal Cancer
Official Title  ICMJE A Pilot Trial Assessing the Feasibility of Delivering Topical MTS-01 to Reduce Dermatitis in Patients Receiving Intensity Modulated Radiation With Concurrent 5-Fluorouracil and Mitomycin-C for Stage I-III Carcinoma of the Anal Canal
Brief Summary

Background:

- Radiation and chemotherapy treatments for anal cancer can cause irritation of the skin that can lead to redness and tenderness, and in some cases can be so severe that it results in blistering or peeling of the skin during treatment. These conditions cause discomfort and may require breaks from radiation treatment. Researchers are interested in determining whether MTS-01, a drug that protects cells and tissues from the effects of radiation, can be given before radiation treatment to prevent these side effects and reduce the irritation of the skin during chemotherapy and radiation for anal cancer.

Objectives:

- To determine the safety and effectiveness of topical MTS-01 given before radiation in the groin and gluteal cleft of patients receiving combined radiation and chemotherapy for anal cancer.

Eligibility:

- Individuals at least 18 years of age who have been diagnosed with cancer of the anal canal and are eligible to receive radiation and chemotherapy treatments.

Design:

  • Participants will be screened with a physical examination, medical history, blood tests, imaging studies and physical examination of the anal canal, and biopsies as needed to evaluate eligibility for treatment.
  • Participants will be scheduled for radiation and chemotherapy treatments on the following schedule:
  • Radiation given 5 days per week for 6 weeks, with topical MTS-01 treatment on the skin in the groin areas and between the buttocks before each treatment
  • Mitomycin C given intravenously on days 1 and 29 of treatment
  • 5-Fluorouracil given intravenously over 4 days (first week and fifth week) during radiation treatment
  • Participants will be monitored throughout the treatment for side effects, with photographs of the treatment area and frequent blood tests.
  • Following the end of radiation, participants will have followup visits for 1 year with blood tests and imaging studies to evaluate the response to treatment.
Detailed Description

Background:

  • Patients with non-metastatic carcinoma of the anal canal are treated with concurrent mitomycin C (MMC), 5-fluorouracil (5-FU), and radiotherapy (RT) in the curative setting in an attempt to preserve the anal sphincter.
  • Radiation dermatitis is a uniform complication of this therapy which frequently results in treatment delay due to pain and discomfort. High grade dermatitis may also become superinfected in the setting of decreased blood counts from chemotherapy and diarrhea from radiation proctitis, further delaying therapy. Approaches that decrease toxicity may be particularly important in patients infected with HIV.
  • MTS-01 (tempol, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is a piperidine nitroxide known to act as a chemical radioprotector with selective protection of normal versus tumor tissue.
  • Tempol gel (tempol 70 mg/mL plus water, ethanol, and hydroxypropyl cellulose) has been evaluated as a topical radioprotector in pilot trials that included a variety of sites.

Objectives:

  • Primary Objective: To determine the safety and tolerability of topical MTS-01 on a daily basis prior to irradiation in the groin and gluteal cleft of patients receiving combined therapy with MMC, 5-FU, and RT for carcinoma of the anal canal.
  • Secondary Objectives will include evaluation of the following endpoints in a preliminary fashion:

    • To describe the rates and severity of skin toxicity in patients treated with this regimen
    • To describe the need for toxicity related treatment breaks with this regimen
    • To describe the opiate requirements in patients treated with this regimen
    • To describe 12-month progression-free survival, disease-free survival, and overall survival in patients treated with concurrent chemotherapy, radiation therapy, and MTS-01
    • Evaluate the effects of antiretroviral therapy, 5-fluorouracil, mitomycin C, and radiation on low level persistent HIV viremia and HIV genetic diversity during therapy and recovery
    • To evaluate the feasibility of collecting HIV RNA and mononuclear cells from rectal associated lymphoid tissue for correlative studies
    • Collect and store anal cytology and core needle biopsies of tumor for future HPV and tumor based analyses

Eligibility:

  • Age greater than or equal to 18 years.
  • ECOG performance status less than or equal to 2.
  • Histologically confirmed carcinoma of the anal canal without evidence of distant metastases
  • No contraindications to definitive chemoradiotherapy for carcinoma of the anal canal

Design:

This is a pilot trial of topical MTS-01 in patients receiving MMC, 5-FU, and IMRT for definitive management of carcinoma of the anal canal. Fifteen patients will be enrolled. MMC will be delivered at a dose of 10mg/m(2) on days 1 and 29. 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. RT will be delivered to a total dose of 50-54 Gy based on tumor characteristics. Tempol gel will be applied to the bilateral groins and the gluteal cleft, avoiding a 3 cm radius from the anal verge, immediately prior to each fraction of RT. RTOG grading will be used to evaluate skin toxicity in both the groin and gluteal cleft weekly during treatment and at 4 weeks, 3 months and 6 months after completion of treatment. The duration of treatment, number of treatment breaks, opiate requirements, and level of pain will be evaluated weekly during treatment and at 4 weeks and 3 months after the completion of treatment. Disease control will be assessed at 4 weeks, 3 months, 6 months, 9 months, and 12 months of follow-up.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Anal Cancer
Intervention  ICMJE
  • Drug: Tempol
    Tempol gel will be applied to the bilateral groins and the gluteal cleft, avoiding a 3 cm radius from the anal verge, immediately prior to each fraction of RT.
  • Drug: 5-Fluorouracil
    5-FU will be delivered as 1000mg/m2/day as 96 hour continuous infusion beginning on day 1 and 29.
  • Drug: Mitomycin-C
    MMC will be delivered at a dose of 10mg/m2 on days 1 and 29
  • Procedure: Radiation Therapy
    RT will be delivered to a total dose of 50-54 Gy based on tumor characteristics.
Study Arms  ICMJE Experimental: 1
Chemo + Radiation
Interventions:
  • Drug: Tempol
  • Drug: 5-Fluorouracil
  • Drug: Mitomycin-C
  • Procedure: Radiation Therapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 16, 2015)
6
Original Estimated Enrollment  ICMJE
 (submitted: March 25, 2011)
15
Actual Study Completion Date  ICMJE April 15, 2015
Actual Primary Completion Date April 15, 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:
  • Histologically proven, invasive primary squamous, basaloid, or cloacogenic carcinoma of the anal canal, stage T1-4, N0-3
  • No previous therapy for anal cancer.
  • Age greater than or equal to 18 years
  • ECOG performance status less than or equal to 2
  • Adequate bone marrow, renal, and hepatic function defined as

    • Absolute neutrophil count greater than or equal to 1,000 cells/mm(3)
    • Platelet count greater than or equal to 100,000/mm(3)
    • Hemoglobin greater than or equal to 8mg/dL
    • Creatinine clearance > 60 mL/min using Cockroft-Gault formula
    • Bilirubin less than or equal to 1.5 times ULN unless, during screening, the patient is receiving protease inhibitor therapy (i.e. indinavir, ritonavir, nelfinavir, and atazanavir) known to be associated with increased bilirubin: in this case total bilirubin less than or equal to 7.5 mg/dl and the direct fraction is less than or equal to 0.7 mg/dl.
    • WBC greater than or equal to 3,000/microL
    • ALT/AST less than or equal to 3 times the upper limit of normal
    • International normalized ratio (INR) less than or equal to 1.5
  • Patients of childbearing potential must be willing to use a medically effective means of birth control for the duration of treatment and six weeks after treatment.
  • Patients must be willing and able to provide informed consent

EXCLUSION CRITERIA:

  • Contraindications to radiotherapy such as a history of prior radiotherapy to the pelvis or a history of inflammatory bowel disease
  • Prior malignancy except:

    • non-melanoma skin cancer
    • controlled Kaposi s Sarcoma (no chemotherapy for KS for 3 months, and no expected need for chemotherapy for the 12-month period of the study)
    • other malignancies with disease free period of at least 3 years
  • Presence of metastatic disease (M1)
  • Co-morbidity that in the estimation of the principal investigator would make the patient unable to tolerate treatment
  • Pregnant or lactating females
  • HIV positive patients with CD4 < 100 cells/mL AND ECOG PS greater than 2.
  • Dermatitis in the anticipated radiation treatment portal.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01324141
Other Study ID Numbers  ICMJE 110129
11-C-0129
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Deborah E Citrin, M.D. National Cancer Institute (NCI)
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date April 15, 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP