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
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- 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)
研究概览
简要总结
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.
详细描述
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
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To describe 12-month progression-free survival, disease-free survival, and overall survival in patients treated with concurrent chemotherapy, radiation therapy, and MTS-01
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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
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To evaluate the feasibility of collecting HIV ribonucleic acid (RNA) and mononuclear cells from rectal associated lymphoid tissue for correlative studies
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Collect and store anal cytology and core needle biopsies of tumor for future human papillomavirus infection (HPV) and tumor based analyses
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
1/Chemo + Radiation
Chemo + Radiation
干预措施: Tempol (Drug)
1/Chemo + Radiation
Chemo + Radiation
干预措施: 5-Fluorouracil (Drug)
1/Chemo + Radiation
Chemo + Radiation
干预措施: Mitomycin-C (Drug)
1/Chemo + Radiation
Chemo + Radiation
干预措施: Radiation Therapy (Procedure)
结局指标
主要结局
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)
时间窗: 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.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE)
时间窗: 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.
次要结局
- 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)
- Number of Participants With Human Immunodeficiency Virus (HIV) in Biopsy Tissue From Rectal Mucosa(Baseline and Course 1 Day 28)
- 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)
- Brief Pain Inventory Score(Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up)
- Duration of Overall Response (DOR)(12 months of follow up, approximately 14 months)
- 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 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)
- 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)
- Pain Interference(Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up)
- Percentage of Total Viable Cells That Were Cluster of Differentiation 3+ (CD3+) Cells in Biopsied Tissue(Baseline and 1 year)
- Mean Percentage Pain Relief After Medication(Baseline, Week 3, Week 6, 1 month follow up, and 3 months follow up)
- 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))
- Overall Survival(start of treatment to time of death, approximately 14 months)
- 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 Tumor Tissue Negative for Human Papilloma Virus (HPV)(Pretreatment)
- Number of Cluster of Differentiation 8+ (CD8) 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(Baseline and 1 year follow up)
- Number of Cluster of Differentiation 4+ (CD4) Cells Per Gram of Biopsied Intestinal Tissue(Baseline and 1 year follow up)
研究者
Deborah Citrin, M.D.
Principal Investigator
National Cancer Institute (NCI)