Neoadjuvant Accelerated Short Course Radiation Therapy With Proton Beam and Capecitabine for Resectable Pancreatic Cancer

Study Overview
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Brief Summary
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A standard treatment for pancreatic cancer is radiation therapy plus chemotherapy after surgery. Radiation therapy and chemotherapy are commonly given for up to six weeks. Previous research has suggested that giving the radiation and chemotherapy for a shorter amount of time (accelerated schedule) before surgery may be better tolerated. In this research study, different schedules of proton radiation therapy will be used. Each schedule will give about the same total dose of radiation. However, the total dose will be spread out over different time periods and different numbers of sessions. The purpose is to find the shortest schedule of radiation therapy that can be given without unacceptable side effects. Proton beam radiation is being used because of its unique ability to deposit its energy directly in the tumor, resulting in less radiation to normal tissue. A new type of PET scan is also being studied to see if it can help predict the response to pre-surgery treatment.

Detailed Description
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Not everyone who participates in this research study will receive the same schedule of radiation therapy. The schedule of radiation therapy will depend on the number of participants enrolled on the study and how well they have tolerated their radiation schedule. All patients will receive proton beam therapy. Here are the proposed schedules of radiation therapy. If at any point too many subjects experience too many unacceptable side effects, no subject will be enrolled to the next level. Dose Level 1: 10 radiation sessions given Monday-Friday for two weeks. Dose Level 2: 5 radiation sessions given Monday, Wednesday and Friday in Week 1 and Tuesday and Thursday in Week 2. Dose Level 3: 5 radiation sessions given Monday, Tuesday, Thursday and Friday in Week 1 and Monday in Week 2. Dose Level 4: 5 Radiation sessions given Monday through Friday in Week 1. In Dose Levels 2, 3 and 4, there are fewer radiation sessions, but the radiation dose given at each session is slightly higher than the dose given in each of the 10 sessions of Dose Level 1. Capecitabine will be given orally (pill form) starting on the first day of radiation therapy and will be taken for the two weeks that the participant receives radiation therapy. On days 1, 8 and 15 of each study cycle, the participant will be seen at the clinic for: physical examination, questions about side effects; and routine blood tests. After the last day of study treatment there will be up to a six-week rest period before surgery is performed. About three to six weeks after the participant has finished study treatment, the following procedures will be done: CT or MRI, physical examination; questions about side effects and blood tests.

Official Title
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Phase I/II of Neoadjuvant Accelerated Short Course Radiation Therapy With Proton Beam and Capecitabine for Resectable Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Procedure: Proton Beam Radiation
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologic of histologic proof of pancreatic ductal carcinoma No evidence of metastatic disease 18 years of age or older ECOG Performance Status of 0 or 1 - Lab values as outlined in the protocol Exclusion Criteria: Tumors in the body or tail of the pancreas Hepatic or peritoneal metastases detected by imaging or laparoscopy prior to chemoradiation Serious concomitant systemic disorders incompatible with the study, such as significant cardiac or pulmonary morbidity, ongoing infection as manifested by fever Pregnant or lactating women Life expectancy of < 3 months Serious, uncontrolled, concurrent infection (s) Prior chemotherapy or radiation for treatment of the patient's pancreatic tumor Clinically significant cardiac disease or myocardial infarction within the last 12 months Other serious uncontrolled medical condition that the investigator feels might compromise study participation Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome Known, existing uncontrolled coagulopathy Any prior fluoropyrimidine therapy Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to a 5-fluorouracil or known DPD deficiency Participation in any investigational drug study within 4 weeks preceding the start of the study History of uncontrolled seizures, central nervous system disorders or psychiatric disability Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery Patients on cimetidine

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>10 Radiation Sessions over 2 weeks | Procedure: Proton Beam Radiation<br>* Given over different schedules and duration<br>Drug: Capecitabine<br>* Given orally starting on day one of radiation therapy for 2 weeks<br>|
| Experimental: Group 2<br>5 Radiation sessions: 3 in week 1 and 2 in week 2 | Procedure: Proton Beam Radiation<br>* Given over different schedules and duration<br>Drug: Capecitabine<br>* Given orally starting on day one of radiation therapy for 2 weeks<br>|
| Experimental: Group 3<br>5 Radiation sessions: 4 in week 1 and 1 in week 2 | Procedure: Proton Beam Radiation<br>* Given over different schedules and duration<br>Drug: Capecitabine<br>* Given orally starting on day one of radiation therapy for 2 weeks<br>|
| Experimental: Group 4<br>5 Radiation Sessions in one week | Procedure: Proton Beam Radiation<br>* Given over different schedules and duration<br>Drug: Capecitabine<br>* Given orally starting on day one of radiation therapy for 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicities in the 5 Radiation Sessions in One Week Arm | The number of participants that experienced a dose limiting toxicity in the arm where radiation was administered over 5 consecutive for a total dose of 25 Gray Equivalents (GyE) (Group 4). Participants were monitored for potential Dose Limiting Toxicities (DLT) for three weeks after the start of radiation. DLTs included: Any grade 3 non-hematologic or hematologic toxicity requiring a greater than 7 day interruption in therapy (excluding alopecia and nausea/vomiting not controlled by optimal supportive care or Any grade 4 non-hematologic toxicity or Any grade 4 neutropenia or thrombocytopenia as defined by Common Terminology Criteria for Adverse Events (CTCAE v3.0) | 3 Weeks | 
| Number of Participants With Grade 3 or Greater Toxicity in Phase II | Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 3). The regimen was considered to be tolerated if less than 20% of participants experienced a grade 3 or greater toxicity. | 30 days after the end of treatment, up to approximately 6 months total | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Pathological Complete Response | All patients that received surgery underwent a full pathological review of their pancreaticoduodenectomy specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th. Initial gross evaluation and identification of resection margins was performed jointly by the surgeon and the pathologist. Pathological complete response will be defined as the absence of any viable tumor cells within the pathologic specimen. | at the time of surgery (28-42 days after start of treatment) | 
| Median Progression Free Survival | The median amount of time from the start of treatment until death or disease progression, whichever occurs first. Progressive Disease (PD): A 20% or greater increase in the sum of Longest Diameter (LD) of all target lesions, taking as reference the smallest sum LD recorded since baseline. | from the start of treatment until death or progression, median duration of 10.4 months | 
| Number of Participants With Surgical Morbidity | Number of participants with pancreatic or any other anastomotic leakage within 30 days of surgery | 30 days post surgery (surgery was 28-42 days after the start of treatment) | 
| 30-Day Post Operative Mortality | The number of participants that died within 30 days of undergoing a pancreaticoduodenectomy. | 30 days after the time of surgery (Surgery is 28-42 days after start of treatment) | 
| Number of Participants With Treatment Related Serious Adverse Events | The number of participants that had treatment related serious adverse events. Adverse events were assessed using Common Terminology Criteria for Adverse Events (CTCAE 3). Adverse events were considered to be serious adverse events if they were grade 3 or greater and were considered to be possibly, probably, or definitely related to treatment. | From the start of treatment until 30 days after the end of treatment, up to approximately 5 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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accelerated short course, proton beam radiation