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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Terminated
• CT.gov ID: NCT01324141
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 48.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anal Cancer	Drug: Tempol; Drug: 5-Fluorouracil; Drug: Mitomycin-C; Procedure: Radiation Therapy	Phase 1

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 human immunodeficiency virus (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 ribonucleic acid (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 human papillomavirus infection (HPV) and tumor based analyses

Eligibility:

• Age greater than or equal to 18 years.

• Eastern Cooperative Oncology Group (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 intensity-modulated radiation therapy (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. Radiation Therapy Oncology Group (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 Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Mar 18, 2011
• Actual Primary Completion Date: Apr 15, 2015
• Actual Study Completion Date: Apr 15, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 1/Chemo + Radiation Chemo + Radiation

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 radiation therapy (RT).; Other Names: MBM-02 ; Drug: 5-Fluorouracil; 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29.; Other Names: 5-FU ; Drug: Mitomycin-C; Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29; Other Names: MMC ; Procedure: Radiation Therapy; Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.; Other Names: RT

Outcome Measures

Primary Outcome Measures

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

   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.

2. Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) [Date treatment consent signed to date off study, approximately, 36 months and 10 days.]

   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.

Secondary Outcome Measures

1. 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]

   RTOG grade 1-5 were used to assess skin toxicity in the groin (right and left inguinal area) and gluteal cleft, as well as two control sites. Grade 0 is no skin toxicity, Grade 1 is follicular, faint or dull erythema, Grade 3 is tender or bright erythema, Grade 3 is confluent, moist desquamation, Grade 4 is ulceration, hemorrhage, or necrosis, and Grade 5 is death due to radiation toxicity.

2. 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 that required a treatment break relative to hematologic (e.g. thrombocytopenia, leukopenia) toxicity (non-dermatologic).

3. 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]

   Opiates are strong drugs prescribed by prescription used for maximum pain relief.

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

   PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST0 version 1.1. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions.

5. Change in the Levels of Number of Human Immunodeficiency Virus (HIV) in the Circulation Pre and Post Treatment [Completion of study, approximately 14 months]

   Change in the levels of number of Human Immunodeficiency Virus (HIV) in the circulation pre and post treatment

6. Ratio of the Number of Cluster of Differentiation 4 (CD4): Cluster of Differentiation 8 (CD8) Cells in the Circulation and Tissue Pre and Post Treatment [Pre-treatment and post treatment tissue (CD4), and pre-treatment and post treatment circulation (CD8)]

   Ratio of the number Cluster of Differentiation 4 (CD4): Cluster of Differentiation 8 (CD8) cells in the circulation and tissue pre and post treatment. The number of cells of CD4 are divided by the number of cells of CD8.

7. Number of Participants With 12 Month Disease Free Survival (DFS) Treated With 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT) [12 months]

   DFS is defined as the duration of time from start of treatment to time of progression. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST0 version 1.1. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions.

8. Overall Survival [start of treatment to time of death, approximately 14 months]

   OS is defined as the duration of time from start of treatment to time of death.

9. Peripheral Blood Mononuclear Cells (Vascular Endothelial Growth Factor (VEGF), Tumor Necrosis Factor Alpha (TNF-alpha), Interleukin-7 (IL-7), and Transforming Growth Factor Beta-1 (TGF-beta1) Cell Counts at Baseline and Course 1 Day 28 [Baseline and Course 1 Day 28]

   Peripheral blood mononuclear cells (Vascular Endothelial Growth Factor (VEGF), Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-7 (IL-7), and Transforming Growth Factor beta-1 (TGF-beta1) were sampled from peripheral blood from rectal associated lymphoid tissue to evaluate immune cell subsets at baseline and after treatment with MTS-0 and 15-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT). It is unknown if a lower or higher numbers has prognostic significance.

10. Number of Participants With Tumor Tissue Negative for Human Papilloma Virus (HPV) [Pretreatment]

    HPV is a sexually transmitted infection that can cause warts and cervical cancer. HPV test detects deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) of HPV in a cell sample (i.e. cervical).

11. Brief Pain Inventory Score [Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up]

    The Brief Pain Inventory Scale is a questionnaire that asks the participant to rate their pain on a scale of 0 (no pain) to 10 (worst pain).

12. Pain Interference [Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up]

    The Brief Pain Inventory Scale questionnaire were used to assess pain interference. Participants rated pain interference on a scale of 0 (does not interfere) to 10 (completely interferes).

13. Mean Percentage Pain Relief After Medication [Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up]

    The Brief Pain Inventory Scale questionnaire were used to assess pain relief after medication. Participants rated pain relief on a scale of 0% (no relief) to 100% (complete relief) and a mean and full range were reported.

14. Duration of Overall Response (DOR) [12 months of follow up, approximately 14 months]

    Duration of overall response is measured from the time measurement criteria are met for Complete Response until the first date that recurrent or progressive disease is objectively document. Complete Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST0 version 1.1. Complete Response is disappearance of all target lesions.

15. Percentage of Total Viable Cells That Were Cluster of Differentiation 3+ (CD3+) Cells in Biopsied Tissue [Baseline and 1 year]

    Percentage of total viable cells that were Cluster of differentiation 3+ (CD3+) cells in biopsied tissue.

16. Absolute Number of Cluster of Differentiation 3+ (CD3) Cells Per Gram of Biopsied Intestinal Tissue [Baseline and 1 year follow up]

    Absolute number of Cluster of differentiation 3+ (CD3) cells per gram of biopsied intestinal tissue. The number of CD3 positive cells were analyzed with flow cytometry of cellular suspensions from biopsy tissue.

17. Number of Cluster of Differentiation 8+ (CD8) Cells Per Gram of Biopsied Intestinal Tissue [Baseline and 1 year follow up]

    Number of Cluster of differentiation 8+ (CD8) cells per gram of biopsied intestinal tissue. The number of CD8 positive cells were analyzed with flow cytometry of cellular suspensions from biopsy tissue.

18. Number of Cluster of Differentiation 4+ (CD4) Cells Per Gram of Biopsied Intestinal Tissue [Baseline and 1 year follow up]

    Number of Cluster of Differentiation 4+ (CD4) cells per gram of biopsied intestinal tissue. The number of CD4 positive cells were analyzed with flow cytometry of cellular suspensions from biopsy tissue.

19. Number of Participants With Human Immunodeficiency Virus (HIV) in Biopsy Tissue From Rectal Mucosa [Baseline and Course 1 Day 28]

    Optional snag biopsies pre and post were collected from participants rectal mucosa to enumerate cell counts.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• 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

• 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

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

• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Deborah E Citrin, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 6, 2014
• Informed Consent Form - Apr 2, 2014

More Information

Publications

• 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.
• 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.
• 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.

• Responsible Party: Deborah Citrin, M.D., Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01324141
• Other Study ID Numbers: 110129; 11-C-0129
• First Posted: Mar 28, 2011
• Last Update Posted: Nov 23, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Deborah Citrin, M.D., Principal Investigator, National Cancer Institute (NCI): Anal Cancer; Radioprotector; Topical; Radiation; Dermatitis
• Additional relevant MeSH terms: Anus Neoplasms; Dermatitis; Fluorouracil; Mitomycins; Mitomycin; Tempol

Study Results

Participant Flow

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Period Title: Overall Study
STARTED	6
COMPLETED	4
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.85 (5.16)
Sex: Female, Male (Count of Participants)
Female	4 66.7%
Male	2 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	6 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 16.7%
White	5 83.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%
Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants)
ECOG 0	3 50%
ECOG 1	2 33.3%
ECOG 2	0 0%
ECOG3	0 0%
ECOG4	0 0%
ECOG 5	0 0%
Human Immunodeficiency Virus (HIV) Status (Count of Participants)
HIV Positive	1 16.7%
HIV Negative	4 66.7%
Human Papilloma Status (Anal Swab) (Count of Participants)
HPV Positive	0 0%
HPV Negative	5 83.3%
T Stage (Count of Participants)
T1	0 0%
T2	2 33.3%
T3	3 50%
T4	0 0%
N Stage (Count of Participants)
N0	4 66.7%
N1	0 0%
N2	0 0%
N3	1 16.7%
Stage (Count of Participants)
I	0 0%
II	4 66.7%
IIIA	0 0%
IIIB	1 16.7%
IV	0 0%

Outcome Measures

1. Primary Outcome

Title	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)
Description	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.
Time Frame	Date treatment consent signed to date off study, approximately, 36 months and 10 days.

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	MTS-01 Grade 1	MTS-01 Grade 2	MTS-01 Grade 3	5FU/MMC/IMRT Grade 2	5-FU/MMC/IMRT Grade 3-4
Arm/Group Description	Grade 1 is mild adverse events.	Grade 2 is moderate adverse events.	Grade 3 is severe adverse events.	Grade 2 is moderate adverse events.	Grade 3 is severe adverse events and Grade 4 is life threatening adverse events.
Measure Participants	5	5	5	5	5
Radiation dermatitis	0	0	0	2	3
Nausea	0	0	0	3	0
Abdominal pain	0	0	0	1	0
Diarrhea	1	1	0	1	2
Gastroesophageal reflux	0	0	0	1	0
Mucositis	0	0	0	1	0
Urinary tract pain	0	0	0	2	0
Bladder spasm	0	0	0	1	0
Urinary incontinence	0	0	0	1	0
Fatigue	1	0	1	1	0
Hypoglycemia	1	0	0	0	0
Transaminitis	0	0	0	1	0
Hypoalbuminemia	0	0	0	1	0
Hypocalcemia	0	0	0	1	0
Myalgia	0	0	0	1	0
Headache	0	0	0	0	1
Syncope	0	0	0	0	1
Infection	0	0	0	1	1
Insomnia	0	0	0	1	0
Pain	0	0	0	2	2
Leukopenia	0	0	0	0	5
Lymphopenia	0	0	0	0	5
Neutropenia	0	0	0	2	3
Febrile neutropenia	0	0	0	0	1
Thrombocytopenia	0	0	0	2	0
Anemia	0	0	0	3	0
Cluster of Differentiation (CD4) count decrease	0	0	1	0	0

2. Primary Outcome

Title	Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)
Description	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.
Time Frame	Date treatment consent signed to date off study, approximately, 36 months and 10 days.

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Count of Participants [Participants]	5 83.3%

3. Secondary Outcome

Title	Mean Grade of Toxicity at Each Timepoint and Location for All Participants Who Underwent Treatment
Description	RTOG grade 1-5 were used to assess skin toxicity in the groin (right and left inguinal area) and gluteal cleft, as well as two control sites. Grade 0 is no skin toxicity, Grade 1 is follicular, faint or dull erythema, Grade 3 is tender or bright erythema, Grade 3 is confluent, moist desquamation, Grade 4 is ulceration, hemorrhage, or necrosis, and Grade 5 is death due to radiation toxicity.
Time Frame	baseline, weeks 1-6, follow up at 1 week, follow up at 2 weeks, and follow up at 4 weeks

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	Gluteal Cleft	Right Inguinal Area	Left Inguinal Area	Left Inguinal Control (C1)	Umbilical Control (C2)
Arm/Group Description	MTS-01 and 5-Fluoruracil (5-FU)/Mitomycin C (MMC) applied to gluteal cleft. Intensity-modulated Radiotherapy (IMRT) administered.	MTS-01 and 5-Fluoruracil (5-FU)/Mitomycin C (MMC) applied to right inguinal area. Intensity-modulated Radiotherapy (IMRT) administered.	MTS-01 and 5-Fluoruracil (5-FU)/Mitomycin C (MMC) applied to left inguinal area. Intensity-modulated Radiotherapy (IMRT) administered.	Control site within the treatment area. Radiation only.	Control site outside of the treatment field. MTS-01 only.
Measure Participants	5	5	5	5	5
Baseline	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Week 1	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Week 2	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Week 3	0.4 (0.5)	0.2 (0.5)	0.2 (0.5)	0.2 (0.5)	0 (0)
Week 4	0.6 (0.5)	0.6 (0.5)	0.6 (0.5)	0.2 (0.5)	0 (0)
Week 5	1 (0.7)	0.8 (0.5)	0.8 (0.5)	0.2 (0.5)	0 (0)
Week 6	1.2 (1.1)	1.2 (0.5)	1.2 (0.5)	0.4 (0.5)	0 (0)
Follow up at 1 week	1.8 (0.8)	1 (0)	1 (0)	0.6 (0.5)	0 (0)
Follow up at 2 weeks	1.2 (0.5)	1 (0)	1 (0)	0.8 (0.5)	0 (0)
Follow up at 4 weeks	0.4 (0.5)	0.2 (0.5)	0.2 (0.5)	0.6 (0)	0 (0)

4. Secondary Outcome

Title	Number of Participants That Required a Treatment Break Relative to Hematologic Toxicity (Non-dermatologic)
Description	Number of participants that required a treatment break relative to hematologic (e.g. thrombocytopenia, leukopenia) toxicity (non-dermatologic).
Time Frame	From beginning until completion of radiation treatment up to 46 days

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Count of Participants [Participants]	0 0%

5. Secondary Outcome

Title	Number of Participants Treated With Topical MTS-01 and 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT) That Required Opiates
Description	Opiates are strong drugs prescribed by prescription used for maximum pain relief.
Time Frame	Completion of study, approximately 14 months after start of treatment

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Count of Participants [Participants]	5 83.3%

6. Secondary Outcome

Title	Number of Participants With 12-month Progression-free Survival Treated With 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT)
Description	PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST0 version 1.1. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Count of Participants [Participants]	4 66.7%

7. Secondary Outcome

Title	Change in the Levels of Number of Human Immunodeficiency Virus (HIV) in the Circulation Pre and Post Treatment
Description	Change in the levels of number of Human Immunodeficiency Virus (HIV) in the circulation pre and post treatment
Time Frame	Completion of study, approximately 14 months

Outcome Measure Data

Analysis Population Description

The participants were screened for HIV before enrollment. Only 1 participant was HIV positive. However, the participant with HIV came off study before post treatment was collected so change cannot be assessed. As pre-specified in the protocol, participants are taken off study for disease progression.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	0

8. Secondary Outcome

Title	Ratio of the Number of Cluster of Differentiation 4 (CD4): Cluster of Differentiation 8 (CD8) Cells in the Circulation and Tissue Pre and Post Treatment
Description	Ratio of the number Cluster of Differentiation 4 (CD4): Cluster of Differentiation 8 (CD8) cells in the circulation and tissue pre and post treatment. The number of cells of CD4 are divided by the number of cells of CD8.
Time Frame	Pre-treatment and post treatment tissue (CD4), and pre-treatment and post treatment circulation (CD8)

Outcome Measure Data

Analysis Population Description

3/6 participants were analyzed because 1 participant was enrolled but withdrew before treatment, samples were collected at the time of optional biopsy which was conducted in 3 patients.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	3
CD4:CD8 Pre-treatment tissue	5.2
CD4:CD8 post treatment tissue	1.89
CD4:CD8 pre-treatment circulation	2.95
CD4:CD8 post treatment circulation	1.56

9. Secondary Outcome

Title	Number of Participants With 12 Month Disease Free Survival (DFS) Treated With 5-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT)
Description	DFS is defined as the duration of time from start of treatment to time of progression. Progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST0 version 1.1. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Count of Participants [Participants]	4 66.7%

10. Secondary Outcome

Title	Overall Survival
Description	OS is defined as the duration of time from start of treatment to time of death.
Time Frame	start of treatment to time of death, approximately 14 months

Outcome Measure Data

Analysis Population Description

This outcome measure could not be completed.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Median (95% Confidence Interval) [months]	NA

11. Secondary Outcome

Title	Peripheral Blood Mononuclear Cells (Vascular Endothelial Growth Factor (VEGF), Tumor Necrosis Factor Alpha (TNF-alpha), Interleukin-7 (IL-7), and Transforming Growth Factor Beta-1 (TGF-beta1) Cell Counts at Baseline and Course 1 Day 28
Description	Peripheral blood mononuclear cells (Vascular Endothelial Growth Factor (VEGF), Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-7 (IL-7), and Transforming Growth Factor beta-1 (TGF-beta1) were sampled from peripheral blood from rectal associated lymphoid tissue to evaluate immune cell subsets at baseline and after treatment with MTS-0 and 15-Fluoruracil (5-FU)/Mitomycin C (MMC)/Intensity-modulated Radiotherapy (IMRT). It is unknown if a lower or higher numbers has prognostic significance.
Time Frame	Baseline and Course 1 Day 28

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
VEGF at baseline	151.24 (45.0)
VEGF at Course 1 Day 28	127.26 (63.6)
TNF-alpha at baseline	3.36 (1.2)
TNF-alpha at Course 1 Day 28	3.21 (2.5)
IL-7 at baseline	11.32 (6.2)
IL-7 at Course 1 Day 28	15.62 (10.3)
TGF-beta 1 at baseline	14435 (3711.7)
TGF-beta 1 at Course 1 Day 28	7946 (2729.3)

12. Secondary Outcome

Title	Number of Participants With Tumor Tissue Negative for Human Papilloma Virus (HPV)
Description	HPV is a sexually transmitted infection that can cause warts and cervical cancer. HPV test detects deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) of HPV in a cell sample (i.e. cervical).
Time Frame	Pretreatment

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Count of Participants [Participants]	5 83.3%

13. Secondary Outcome

Title	Brief Pain Inventory Score
Description	The Brief Pain Inventory Scale is a questionnaire that asks the participant to rate their pain on a scale of 0 (no pain) to 10 (worst pain).
Time Frame	Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Worst pain at baseline	4.8
Worst pain at treatment week 3	3.5
Worst pain at treatment week 6	7.2
Worst pain at 1 month follow up	3.1
Worst pain at 3 months follow up	2.1
Least pain at baseline	1.4
Least pain at treatment week 3	1.5
least pain at treatment week 6	3.6
Least pain at 1 month follow up	1.2
Least pain at 3 months follow up	2.8
Average pain at baseline	1.8
Average pain at treatment week 3	1.9
Average pain at treatment week 6	5.0
Average pain at 1 month follow up	2.0
Average pain at 3 months follow up	3.0
Pain at time of survey at baseline	1.6
Pain at time of survey at treatment week 3	1.3
Pain at time of survey at treatment week 6	5.4
Pain at time of survey a 1 month follow up	2.2
Pain at time of survey at 3 months follow up	2.2

14. Secondary Outcome

Title	Pain Interference
Description	The Brief Pain Inventory Scale questionnaire were used to assess pain interference. Participants rated pain interference on a scale of 0 (does not interfere) to 10 (completely interferes).
Time Frame	Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Pain interference at baseline	1.73
Pain interference at treatment week 3	3.00
Pain interference at treatment week 6	6.70
Pain interference at 1 month follow up	3.17
Pain interference at 3 months follow up	1.87

15. Secondary Outcome

Title	Mean Percentage Pain Relief After Medication
Description	The Brief Pain Inventory Scale questionnaire were used to assess pain relief after medication. Participants rated pain relief on a scale of 0% (no relief) to 100% (complete relief) and a mean and full range were reported.
Time Frame	Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Baseline	90.0
Treatment week 3	93.8
Treatment week 6	44.0
1 month follow up	89.0
3 months follow up	83.0

16. Secondary Outcome

Title	Duration of Overall Response (DOR)
Description	Duration of overall response is measured from the time measurement criteria are met for Complete Response until the first date that recurrent or progressive disease is objectively document. Complete Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST0 version 1.1. Complete Response is disappearance of all target lesions.
Time Frame	12 months of follow up, approximately 14 months

Outcome Measure Data

Analysis Population Description

This outcome measure was not measurable.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Median (95% Confidence Interval) [months]	NA

17. Secondary Outcome

Title	Percentage of Total Viable Cells That Were Cluster of Differentiation 3+ (CD3+) Cells in Biopsied Tissue
Description	Percentage of total viable cells that were Cluster of differentiation 3+ (CD3+) cells in biopsied tissue.
Time Frame	Baseline and 1 year

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment. 3 participants underwent optional biopsy.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	3
Baseline	7.93
1 year	4.40

18. Secondary Outcome

Title	Absolute Number of Cluster of Differentiation 3+ (CD3) Cells Per Gram of Biopsied Intestinal Tissue
Description	Absolute number of Cluster of differentiation 3+ (CD3) cells per gram of biopsied intestinal tissue. The number of CD3 positive cells were analyzed with flow cytometry of cellular suspensions from biopsy tissue.
Time Frame	Baseline and 1 year follow up

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment. 3 participants underwent optional biopsy.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	3
Baseline	22.98
1 year follow up	13.62

19. Secondary Outcome

Title	Number of Cluster of Differentiation 8+ (CD8) Cells Per Gram of Biopsied Intestinal Tissue
Description	Number of Cluster of differentiation 8+ (CD8) cells per gram of biopsied intestinal tissue. The number of CD8 positive cells were analyzed with flow cytometry of cellular suspensions from biopsy tissue.
Time Frame	Baseline and 1 year follow up

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment. 3 participants underwent optional biopsy.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	3
Baseline	4.8
1 year follow up	4.0

20. Secondary Outcome

Title	Number of Cluster of Differentiation 4+ (CD4) Cells Per Gram of Biopsied Intestinal Tissue
Description	Number of Cluster of Differentiation 4+ (CD4) cells per gram of biopsied intestinal tissue. The number of CD4 positive cells were analyzed with flow cytometry of cellular suspensions from biopsy tissue.
Time Frame	Baseline and 1 year follow up

Outcome Measure Data

Analysis Population Description

1/6 participants enrolled withdrew before treatment.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	5
Baseline	17.64
1 year follow up	12.72

21. Secondary Outcome

Title	Number of Participants With Human Immunodeficiency Virus (HIV) in Biopsy Tissue From Rectal Mucosa
Description	Optional snag biopsies pre and post were collected from participants rectal mucosa to enumerate cell counts.
Time Frame	Baseline and Course 1 Day 28

Outcome Measure Data

Analysis Population Description

This outcome measure could not be completed. 1/6 participants enrolled withdrew before treatment. No participants with HIV ribonucleic acid (RNA) underwent optional biopsy. HIV RNA is not analyzed unless a patient has HIV. Thus, data not collected.

Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
Measure Participants	0

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately, 36 months and 10 days.
Adverse Event Reporting Description	1/6 participants enrolled withdrew before treatment.
Arm/Group Title	1/Chemo + Radiation
Arm/Group Description	Chemo + Radiation 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 radiation therapy (RT). 5-Fluorouracil: 5-FU will be delivered as 1000mg/m(2)/day as 96 hour continuous infusion beginning on day 1 and 29. Mitomycin-C: Mitomycin-C (MMC) will be delivered at a dose of 10mg/m(2) on days 1 and 29 Radiation Therapy: Radiation therapy (RT) will be delivered to a total dose of 50-54 Gray (Gy) based on tumor characteristics.
All Cause Mortality
	1/Chemo + Radiation
	Affected / at Risk (%)	# Events
Total	0/5 (0%)
Serious Adverse Events
	1/Chemo + Radiation
	Affected / at Risk (%)	# Events
Total	3/5 (60%)
General disorders
Fever	1/5 (20%)	1
Infections and infestations
Skin infection	1/5 (20%)	1
Investigations
Febrile neutropenia	2/5 (40%)	2
Neutrophil count decreased	1/5 (20%)	1
Metabolism and nutrition disorders
Dehydration	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/5 (20%)	1
Vascular disorders
Hypotension	1/5 (20%)	1
Thromboembolic event	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	1/Chemo + Radiation
	Affected / at Risk (%)	# Events
Total	5/5 (100%)
Blood and lymphatic system disorders
Anemia	4/5 (80%)	8
Eye disorders
Blurred vision	2/5 (40%)	2
Photophobia	1/5 (20%)	1
Gastrointestinal disorders
Abdominal pain	2/5 (40%)	4
Anal hemorrhage	1/5 (20%)	1
Anal pain	1/5 (20%)	2
Constipation	2/5 (40%)	2
Diarrhea	4/5 (80%)	14
Dry mouth	2/5 (40%)	2
Dyspepsia	1/5 (20%)	1
Fecal incontinence	1/5 (20%)	2
Flatulence	3/5 (60%)	5
Gastroesophageal reflux disease	1/5 (20%)	1
Gastrointestinal disorders - Other, Tongue deviation	1/5 (20%)	1
Hemorrhoidal hemorrhage	1/5 (20%)	1
Mucositis oral	3/5 (60%)	4
Nausea	4/5 (80%)	8
Oral dysesthesia	1/5 (20%)	1
Rectal pain	1/5 (20%)	1
Vomiting	2/5 (40%)	3
General disorders
Chills	2/5 (40%)	3
Fatigue	5/5 (100%)	8
Fever	1/5 (20%)	1
Infections and infestations
Mucosal infection	2/5 (40%)	2
Skin infection	1/5 (20%)	2
Urinary tract infection	1/5 (20%)	2
Injury, poisoning and procedural complications
Dermatitis radiation	5/5 (100%)	19
Investigations
Alanine aminotransferase increased	4/5 (80%)	7
Alkaline phosphatase increased	1/5 (20%)	1
Aspartate aminotransferase increased	3/5 (60%)	4
CD4 lymphocytes decreased	1/5 (20%)	1
Lymphocyte count decreased	5/5 (100%)	34
Neutrophil count decreased	5/5 (100%)	15
Platelet count decreased	5/5 (100%)	10
White blood cell decreased	5/5 (100%)	22
Metabolism and nutrition disorders
Anorexia	1/5 (20%)	1
Hyperglycemia	2/5 (40%)	2
Hypermagnesemia	2/5 (40%)	2
Hypoalbuminemia	5/5 (100%)	8
Hypocalcemia	1/5 (20%)	1
Hypoglycemia	1/5 (20%)	1
Hyponatremia	1/5 (20%)	1
Musculoskeletal and connective tissue disorders
Bone pain	1/5 (20%)	1
Myalgia	1/5 (20%)	2
Nervous system disorders
Dizziness	2/5 (40%)	2
Headache	3/5 (60%)	8
Memory impairment	1/5 (20%)	1
Syncope	1/5 (20%)	1
Psychiatric disorders
Insomnia	3/5 (60%)	3
Renal and urinary disorders
Bladder spasm	1/5 (20%)	1
Urinary frequency	3/5 (60%)	3
Urinary incontinence	1/5 (20%)	1
Urinary tract pain	4/5 (80%)	7
Urinary urgency	1/5 (20%)	1
Reproductive system and breast disorders
Ejaculation disorder	1/5 (20%)	2
Perineal pain	2/5 (40%)	4
Vaginal pain	1/5 (20%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/5 (20%)	2
Skin and subcutaneous tissue disorders
Alopecia	2/5 (40%)	2
Pain of skin	1/5 (20%)	2
Pruritus	2/5 (40%)	2
Skin and subcutaneous tissue disorders - Other, Clamminess	1/5 (20%)	1
Skin and subcutaneous tissue disorders	1/5 (20%)	1
Skin and subcutaneous tissue disorders - Other, carbunkle	1/5 (20%)	1
Skin and subcutaneous tissue disorders - Other, sweating	1/5 (20%)	1
Vascular disorders
Hot flashes	1/5 (20%)	1
Hypotension	1/5 (20%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.