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

NCT ID: NCT00889187

Last Updated: 2018-05-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-12-31
• Study Completion Date: 2011-12-30

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

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Cohort 1: Photon Rad (30 Gy/12 days)+Capecitabine

Neoadjuvant Short-Course Photon Radiation:

At dose level 1, a total dose of 30 Gy in 10 fractions (3 Gy/day) was prescribed to the 95% isodose and administered 5 days per week over 12 days.

Chemotherapy:

Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.

Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.

Group Type: EXPERIMENTAL

Neoadjuvant Short-Course Photon Radiation

Intervention Type: RADIATION

Capecitabine

Intervention Type: DRUG

Phase I Cohort 2: Photon Rad (25 Gy/11 days)+Capecitabine

Neoadjuvant Short-Course Photon Radiation:

At dose level 2, a total dose of 25 Gy in 5 fractions was prescribed to the 95% isodose and administered at 5 Gy per fraction over 11 days.

Chemotherapy:

Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.

Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.

Group Type: EXPERIMENTAL

Neoadjuvant Short-Course Photon Radiation

Intervention Type: RADIATION

Capecitabine

Intervention Type: DRUG

Phase I Cohort 3: Photon Rad (25 Gy/5 days)+Capecitabine

Neoadjuvant Short-Course Photon Radiation:

At dose level 3, a total dose of 25 Gy in 5 fractions was prescribed to the 95% isodose and administered at 5 Gy per fraction over 5 days.

Chemotherapy:

Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.

Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.

Group Type: EXPERIMENTAL

Neoadjuvant Short-Course Photon Radiation

Intervention Type: RADIATION

Capecitabine

Intervention Type: DRUG

All Phase I: Photon Rad+Capecitabine

Neoadjuvant Short-Course Photon Radiation:

All Phase I participants received the radiation regimen according to the established dose escalation schedule.

Chemotherapy:

Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.

Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.

Group Type: EXPERIMENTAL

Neoadjuvant Short-Course Photon Radiation

Intervention Type: RADIATION

Capecitabine

Intervention Type: DRUG

Phase II: Photon Rad (MTD)+Capecitabine

Neoadjuvant Short-Course Photon Radiation:

Phase II participants received the radiation regimen established in the Phase I study (MTD).

Chemotherapy:

Capecitabine was given orally 825 mg/m2 BID (total 1650 mg/m2 per day) for ten consecutive weekdays, beginning on the morning of the first day of radiation therapy.

Patients underwent resection of their pancreatic cancer 1-3 weeks after the completion of chemoradiation. It was recommended that patients undergoing R0 or R1 resections receive adjuvant treatment with 4-6 cycles of gemcitabine-based therapy per institutional policy, to start 4 to 10 weeks after the operation.

Group Type: EXPERIMENTAL

Neoadjuvant Short-Course Photon Radiation

Intervention Type: RADIATION

Capecitabine

Intervention Type: DRUG

Interventions

Neoadjuvant Short-Course Photon Radiation

Intervention Type: RADIATION

Capecitabine

Intervention Type: DRUG

Other Intervention Names

Xeloda

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Harvey Mamon, MD, PhD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Harvey Mamon, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber/Brigham and Women's Cancer Center

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 24231241 (View on PubMed)

Other Identifiers

08-375

Identifier Type: -

Identifier Source: org_study_id