Clinical trial NCT00889187: Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer
Official title: Phase I/II Study of Neoadjuvant Accelerated Short Course Radiation Therapy With Photons and Capecitabine for Resectable Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Keywords: radiation therapy
capecitabine
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Brigham and Women's Hospital
name: Massachusetts General Hospital
First posted: 2009-04-28
Enrollment: 10
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: The purpose of this research study is to determine if it is possible to deliver high dose radiation in one week while also giving the drug capecitabine for the treatment of pancreatic cancer prior to surgery, to determine if this treatment can be given safely for the treatment of pancreatic cancer prior to surgery and, to determine if this treatment can improve the local control pancreatic cancer prior to surgery compared to historical controls of standard treatment.

Detailed description: OBJECTIVES:

Primary

* Phase I: To determine the feasibility and tolerability of radiation therapy for pancreatic cancer delivered with high dose external beam radiation in a one week accelerated schedule with concurrent capecitabine
* Phase II: To demonstrate a grade 3 or greater (any) toxicity rate of less than 20%

Secondary

* To determine local control and recurrence patterns of pancreatic cancer relative to a standard regimen of 50.4 Gy as seen in historical controls
* To determine the pathologic response rate
* To determine the progression-free survival
* To determine the surgical morbidity
* To determine 30-day post-operative mortality after pancreatic resection

Eligibility criteria: Inclusion Criteria:

* Cytologic or histologic proof of pancreatic ductal carcinoma is required prior to treatment.
* No evidence of metastatic disease as determined by chest CT scan, abdominal CT scan (or MRI with gadolinium and/or manganese), and all patients must be staged with a physical exam, chest CT, and abdominal CT with intravenous contrast.
* Only potentially resectable patients are eligible. Potentially resectable is defined as: a)no extrapancreatic disease, b)no evidence (on CT) of involvement of the celiac axis or superior mesenteric artery, and c)no evidence (on CT or MRI) of occlusion of the superior mesenteric vein or superior mesenteric-portal venous confluence.
* 18 years of age or older
* ECOG Performance status of 0 or 1
* Women of child bearing potential must practice adequate contraception and to refrain from breast feeding. Female patients must have a negative pregnancy test within 7 days of treatment
* Lab values as specified in the protocol

Exclusion Criteria:

* Patients cannot have 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, or ongoing infection as manifested by fever
* Pregnant or lactating women
* Life expectancy \< 3 months
* Serious, uncontrolled, concurrent infection(s)
* Any prior chemotherapy or radiation for treatment of the patient's pancreatic tumor
* Treatment for other cancers within the last five years, except cured non-melanoma skin cancer and treated in situ cervical cancer
* Clinically significant cardiac disease or myocardial infarction within the last 12 months
* Other serious uncontrolled medical conditions that the investigator feels might compromise study participation
* Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
* Known, existing uncontrolled coagulopathy
* Unwillingness to participate or inability to comply with the protocol for the duration of the study
* Any prior fluoropyrimidine therapy (unless given in an adjuvant setting and completed at least 6 months earlier)
* Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known DPD deficiency
* Participation in any investigational drug study within 4 weeks preceding the start of study treatment
* History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake
* Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery
* Patients should not be on cimetidine as it can decrease the clearance of 5-FU. Another H2-blocker or proton pump inhibitor may be substituted before study entry

Primary outcomes:
measure: Neoadjuvant Short-Course Photon Radiation Therapy Maximum Tolerated Dose (MTD) [Phase I]
timeFrame: within 3 weeks of the start of chemoradiation therapy
measure: Dose Limiting Toxicity (DLT) [Phase I]
timeFrame: within 3 weeks of the start of chemoradiation therapy
measure: Grade 3-5 Toxicity Rate [Phase II]
timeFrame: within 3 weeks of the start of chemoradiation therapy
Secondary outcomes:
measure: Local Recurrence Rate [Phase II]
timeFrame: Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.
measure: Pathologic Response Rate [Phase II]
timeFrame: Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
measure: Progression-Free Survival (PFS) [Phase II]
timeFrame: Disease was assessed radiologically at baseline and after treatment every 6 months for first 2 years and annually in years 3-5.
measure: Surgical Morbidity Rate [Phase II]
timeFrame: Assessed after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
measure: Surgical Mortality Rate [Phase II]
timeFrame: Assessed up to 30 days after resection; Patients underwent resection of their pancreatic cancer up to 3 weeks after completion of chemoradiation therapy
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
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: Dana-Farber/Brigham and Women's Cancer Center
name: Harvey Mamon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wo JY, Mamon HJ, Ferrone CR, Ryan DP, Blaszkowsky LS, Kwak EL, Tseng YD, Napolitano BN, Ancukiewicz M, Swanson RS, Lillemoe KD, Fernandez-del Castillo C, Hong TS. Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer. Radiother Oncol. 2014 Jan;110(1):160-4. doi: 10.1016/j.radonc.2013.10.027. Epub 2013 Nov 11.