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

NCT01324141 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 11012911-C-0129
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Anal Cancer

Keywords

Anal Cancer; Radioprotector; Topical; Radiation; Dermatitis

Outcome Measures

Primary Outcomes (2)

• Number of Grade 1 and Higher Adverse Events Possibly, Probably, or Definitely Related to Topical MTS-01 and 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT)

  Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life threatening, and Grade 5 is death related to adverse event.

  Date treatment consent signed to date off study, approximately, 36 months and 10 days.

• Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)

  Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

  Date treatment consent signed to date off study, approximately, 36 months and 10 days.

Secondary Outcomes (19)

• Mean Grade of Toxicity at Each Timepoint and Location for All Participants Who Underwent Treatment

  baseline, weeks 1-6, follow up at 1 week, follow up at 2 weeks, and follow up at 4 weeks

• Number of Participants That Required a Treatment Break Relative to Hematologic Toxicity (Non-dermatologic)

  From beginning until completion of radiation treatment up to 46 days

• Number of Participants Treated With Topical MTS-01 and 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT) That Required Opiates

  Completion of study, approximately 14 months after start of treatment

• Number of Participants With 12-month Progression-free Survival Treated With 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT)

  12 months

• Change in the Levels of Number of Human Immunodeficiency Virus (HIV) in the Circulation Pre and Post Treatment

  Completion of study, approximately 14 months

Study Arms (1)

1/Chemo + Radiation

EXPERIMENTAL

Chemo + Radiation

Drug: Tempol; Drug: 5-Fluorouracil; Drug: Mitomycin-C; Procedure: Radiation Therapy

Interventions

Tempol DRUG

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 radiation therapy (RT).

Also known as: MBM-02

1/Chemo + Radiation

5-Fluorouracil DRUG

5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29.

Also known as: 5-FU

1/Chemo + Radiation

Mitomycin-C DRUG

Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29

Also known as: MMC

1/Chemo + Radiation

Radiation Therapy PROCEDURE

Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.

Also known as: RT

1/Chemo + Radiation

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Eastern Cooperative Oncology Group (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 Cockcroft-Gault formula
• Bilirubin less than or equal to 1.5 times upper limit of normal (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.
• White blood cell (WBC) greater than or equal to 3,000/microL
• Alanine aminotransferase (ALT)/aspartate aminotransferase (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

You may not qualify if:

• 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
• Human immunodeficiency virus (HIV) positive patients with cluster of differentiation 4 (CD4) \< 100 cells/mL AND ECOG performance status (PS) greater than 2.
• Dermatitis in the anticipated radiation treatment portal.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009 Jul-Aug;59(4):225-49. doi: 10.3322/caac.20006. Epub 2009 May 27.

  PMID: 19474385 BACKGROUND

• Bower M, Powles T, Newsom-Davis T, Thirlwell C, Stebbing J, Mandalia S, Nelson M, Gazzard B. HIV-associated anal cancer: has highly active antiretroviral therapy reduced the incidence or improved the outcome? J Acquir Immune Defic Syndr. 2004 Dec 15;37(5):1563-5. doi: 10.1097/00126334-200412150-00004.

  PMID: 15577408 BACKGROUND

• Crum-Cianflone NF, Hullsiek KH, Marconi VC, Ganesan A, Weintrob A, Barthel RV, Agan BK; Infectious Disease Clinical Research Program HIV Working Group. Anal cancers among HIV-infected persons: HAART is not slowing rising incidence. AIDS. 2010 Feb 20;24(4):535-43. doi: 10.1097/QAD.0b013e328331f6e2.

  PMID: 19926961 BACKGROUND

MeSH Terms

Conditions

Anus Neoplasms; Dermatitis

Interventions

tempol; Fluorouracil; Mitomycin; Radiotherapy

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Mitomycins; Indolequinones; Quinones; Organic Chemicals; Azirines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics

Results Point of Contact

• Title: Dr. Deborah E. Citrin
• Organization: National Cancer Institute

citrind@mail.nih.gov

301-496-5457

Study Officials

• Deborah E Citrin, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 25, 2011
• First Posted: March 28, 2011
• Study Start: March 18, 2011
• Primary Completion: April 15, 2015
• Study Completion: April 15, 2015
• Last Updated: November 23, 2021
• Results First Posted: November 23, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)