Topical MTS-01 for Dermatitis During Radiation and Chemotherapy for Anal Cancer
| Status: | Terminated |
|---|---|
| Conditions: | Colorectal Cancer, Cancer, Dermatology |
| Therapuetic Areas: | Dermatology / Plastic Surgery, Oncology |
| Healthy: | No |
| Age Range: | 18 - 90 |
| Updated: | 6/2/2017 |
| Start Date: | March 18, 2011 |
| End Date: | April 15, 2015 |
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
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.
- 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.
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.
- 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.
- 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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