Concurrent Chemoradiation + 5-FU + Mitomycin-C in Anal Carcinoma

Study Overview
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Brief Summary
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This research study is a Pilot Study. Pilot studies are conducted to see if it is practical to do this type of research ona larger scale in the future. The pilot part of the study is to assess the possibility of using pencil beam proton radiation to treat your type of cancer. Proton radiation is used for many other types of malignancies, but its use for the treatment of anal cancer has been limited. The treatment is still being studied as research doctors are trying to find out more about its use in the treatment of anal cancer. Proton beam radiation therapy is an FDA approved radiation delivery system. You are being asked to participate in this study because you have cancer in the anal canal. Conventional radiation therapy with photons in combination with 5-FU and mitomycin-C is used as standard treatment for many patients with anal cancer. In this research study we are looking at another type of radiation called proton radiation, which is known to spare surrounding tissue and organs from radiation. Proton radiation delivers radiation to the area requiring radiation but delivers no dose beyond the region requiring treatment. There are several techniques that can be used to deliver proton radiation therapy. One of the newer techniques, called pencil beam scanning, allows for more accurate delivery of radiation to your tumor and further reduces the amount of normal tissue exposed to radiation. Most proton patients are treated with a number of beams that study doctors conform to the shape of your tumor. Pencil beam scanning delivers radiation with a single, narrow proton beam that is swept over the area of your tumor. This may reduce side effects that patients would normally experience with conventional radiation therapy or other means of delivering proton radiation therapy, and also minimizes treatment time. In this research study, we are evaluating the effectiveness of using pencil beam proton radiation delivered to reduce side effects associated with radiation treatment.

Detailed Description
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If you agree to participate in this study, you will be asked to undergo some screening tests or procedures to confirm that you are eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if it turns out that you do not take part in the research study. If you have had some of these tests or procedures recently, they may or may not have to be repeated. The screening will include the following: a medical history, physical examination, biopsy of your tumor, anal and groin exam, archival tumor tissue, CT or PET-CT, MRI, blood tests and a serum pregnancy test. If these tests show that you are eligible to participate in the research study, you will begin the study treatment. If you do not meet the eligibility criteria, you will not be able to participate in this research study. Proton Radiation will be delivered daily for 5-6 weeks, depending on the dose prescribed by your physician. Treatment is delivered (Monday-Friday) for 5 days (no weekends or holidays). Each treatment will require that you lie on a table for 25-30 minutes. You will receive radiation therapy as an outpatient at the Massachusetts General Hospital. You will start receiving chemotherapy within 5 days of starting radiation treatment. The day you start chemotherapy will be considered Day 1. You will receive Mitomycin-C on Days 1 and 29 of chemotherapy. Mitomycin-C will be delivered via IV infusion over a period of 10-30 minutes. You will receive 5-fluorouracil on Day 1 and 29 of chemotherapy. You will be fitted with an ambulatory infusion pump that will administer 5-FU via IV infusion continuously over a period of 96 hours. The infusion pump will be about the size of a paperback book that can fit into a front-pack or fanny-pack around your waist. This pump will be connected to your body. The nurses in the infusion room will start the pump and disconnect it after 4 days. At your 6 and 12 week follow up visits, a physical examination and the tests and procedures you receive will tell your study doctor whether your disease has gotten better, worse or stayed the same. If your cancer has gotten better, you will continue to be monitored at your follow up visits. If your cancer is suspected to have gotten worse, you will need to have a biopsy to confirm. If the biopsy is negative, you will need to come back for re-evaluation at 16 weeks (about 4 months) after completing radiation therapy. If the biopsy confirms that your cancer has gotten worse, your doctor will recommend that you have surgery for the removal of your tumor. If your cancer has stayed the same, your doctor will recommend that you have additional procedures done to develop a plan for treatment. After you complete radiation therapy, you will be followed for up to 5 years.

Official Title
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A Pilot Feasibility Study of Definitive Concurrent Chemoradiation With Pencil Beam Scanning Proton Beam in Combination With 5-Fluorouracil and Mitomycin-C for Carcinoma of the Anal Canal

Conditions
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Carcinoma of the Anal Canal

Intervention / Treatment
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* Radiation: Pencil Beam scanning Radiation
* Drug: 5-fluorouracil
* Drug: Mitomycin-C


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed invasive primary squamous, basaloid or cloacogenic carcinoma of the anal canal Life expectancy of at least 3 months Exclusion Criteria: Prior abdominopelvic radiotherapy Prior systemic therapy for anal cancer Pregnant or breastfeeding Receiving other investigational agents History of allergic reactions attributed to compounds of similar chemical or biologic composition to mitomycin-C or 5-fluorouracil Prior surgery for cancer of the anus that removed all macroscopic anal cancer Uncontrolled intercurrent illness AIDS based on current CDC definition Other immunocompromised status Individuals with a history of a different malignancy are ineligible except for the following circumstances: disease-free for at least 5 years or at low risk for recurrence or cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pencil Beam Scanning Radiation<br>Pencil Beam Radiation daily, Monday-Friday, for 5-6 weeks Mitomycin-C via IV on Days 1 and 29 5-Fluorouracil via infusion pump over 4 days, starting Day 1 and 29 of chemotherapy | Radiation: Pencil Beam scanning Radiation<br> <br> Drug: 5-fluorouracil<br> <br> * Other names: 5-FU;Drug: Mitomycin-C<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of administration of pencil beam scanning proton beam radiation with chemotherapy for anal cancer | The primary objective of this study is to determine feasibility of administration of pencil beam scanning proton beam radiotherapy in combination with concurrent 5-fluorouracil (5-FU) and mitomycin-C for carcinoma of the anal canal. Proton radiotherapy will be considered feasible if grade 3+ skin toxicity seen on this protocol is less than 48% (reported grade 3+ dermatologic toxicity from RTOG 98-11) | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Adverse Events | To assess rates of grade 3+ acute toxicities in the first 90 days following the start of combined modality treatment. To evaluate adverse events associated with the treatment regimens after 90 days from the start of combined modality treatment. | 2 years | 
| Quality of Life Outcomes | To assess health related quality-of-life outcomes after proton radiotherapy for anal carcinoma using objective measurements and validated quality-of-life instruments. Health quality of life questionnaire will be completed before treatment, within 2 weeks of completion of radiotherapy and quarterly for 15 months. | 2 years | 
| Clinical Complete Response | Estimate the clinical complete response rate at 6 weeks and 12 weeks after completion of treatment. | 12 weeks | 
| Radiotherapy treatment time | Evaluate elapsed time form radiotherapy treatment start to radiotherapy treatment end | 2 years | 
| Local-regional failure | Estimate the rate of local-regional failure; local-regional failure will be measured from study entry to date of first local or regional failure | 2 years | 
| Colostomy Failure and Colostomy-Free Survival | Estimate the rate of colostomy failure; colostomy failure will be measured from study entry to date of colostomy failure. Estimate the rate of colostomy-free survival; colostomy-free survival will be measured from study entry. | 2 years | 
| Disease-free Survival | Estimate the rate of disease-free survival; disease-free survival will be measured from study entry to date of first local, regional, distant or second primary failure or date of death. | 2 years | 
| Overall Survival | Estimate the rate of overall survival; overall survival will be measured from study entry to date of death. | 2 years | 
| Correlative Studies | Evaluate prevalence and prognostic significance of Bcl-2, Bcl-X1, HPV | 2 years | 
| To describe mood in the study population | To describe QOL and mood in this study population to help us better identify the side effects and challenges faced by patients. | 2 years | 
| To measure utilization of health services | To measure utilization of health services (emergency room, hospital and intensive care unit) in the study population. | 2 years |