Clinical trial NCT00438256: Neoadjuvant Accelerated Short Course Radiation Therapy With Proton Beam and Capecitabine for Resectable Pancreatic Cancer
Official title: Phase I/II of Neoadjuvant Accelerated Short Course Radiation Therapy With Proton Beam and Capecitabine for Resectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: accelerated short course
proton beam radiation
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
name: National Cancer Institute (NCI)
First posted: 2007-02-22
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: * 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities in the 5 Radiation Sessions in One Week Arm
timeFrame: 3 Weeks
measure: Number of Participants With Grade 3 or Greater Toxicity in Phase II
timeFrame: 30 days after the end of treatment, up to approximately 6 months total
Secondary outcomes:
measure: Number of Participants With a Pathological Complete Response
timeFrame: at the time of surgery (28-42 days after start of treatment)
measure: Median Progression Free Survival
timeFrame: from the start of treatment until death or progression, median duration of 10.4 months
measure: Number of Participants With Surgical Morbidity
timeFrame: 30 days post surgery (surgery was 28-42 days after the start of treatment)
measure: 30-Day Post Operative Mortality
timeFrame: 30 days after the time of surgery (Surgery is 28-42 days after start of treatment)
measure: Number of Participants With Treatment Related Serious Adverse Events
timeFrame: From the start of treatment until 30 days after the end of treatment, up to approximately 5 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Theodore Hong, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hong TS, Ryan DP, Borger DR, Blaszkowsky LS, Yeap BY, Ancukiewicz M, Deshpande V, Shinagare S, Wo JY, Boucher Y, Wadlow RC, Kwak EL, Allen JN, Clark JW, Zhu AX, Ferrone CR, Mamon HJ, Adams J, Winrich B, Grillo T, Jain RK, DeLaney TF, Fernandez-del Castillo C, Duda DG. A phase 1/2 and biomarker study of preoperative short course chemoradiation with proton beam therapy and capecitabine followed by early surgery for resectable pancreatic ductal adenocarcinoma. Int J Radiat Oncol Biol Phys. 2014 Jul 15;89(4):830-8. doi: 10.1016/j.ijrobp.2014.03.034. Epub 2014 May 24.