Phase II Gemcitabine + Fractionated Stereotactic Radiotherapy for Unresectable Pancreatic Adenocarcinoma
|ClinicalTrials.gov Identifier: NCT01146054|
Recruitment Status : Completed
First Posted : June 17, 2010
Results First Posted : May 15, 2017
Last Update Posted : December 19, 2017
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Cancer||Device: CyberKnife based stereotactic radiotherapy Drug: Gemcitabine Drug: Fludeoxyglucose (18F) (FDG)||Phase 2|
Treatment on this protocol requires placement of 3-5 gold (99.9% pure, 1-5 mm length, or visicoils) fiducials for targeting purposes. The fiducials will be used as surrogates for targeting the daily tumor position during treatment. The fiducials will be placed directly into the tumor and/or periphery under endoscopic ultrasound or CT guidance. Gemcitabine prior to SBRT is optional. If given, up to 3 weeks in a 6-week period is allowable, and may be given prior to study enrollment. Administration should be on a 3-week on, 1-week off schedule, weekly at 1,000 mg/m2. Simulation should be done 5 days or more following placement of fiducials. For simulation patients will be positioned supine in an Alpha Cradle or equivalent immobilization device will be custom made for each patient. Standard free-breathing CT and respiratory-correlated 4-D pancreatic protocol CT will be obtained on each patient The 4D-CT scan will be used for characterizing target motion during quiet respiration. Following simulation, patients may be treated either in a respiratory gated (Trilogy, Elekta, Novalis) or a respiratory tracking (Cyberknife) manner. The selection of which radiotherapy treatment machine to use is left to each investigator. All patients will receive 5 fractions of 6.6 Gy delivered over a five-day period. Ideally all 5 fractions should be delivered Monday through Friday, however it may be delivered over 2 weeks as long as the patient receives at least 2 fractions a week. Gemcitabine, cycles should resume up to 4 weeks following SBRT on a 3-week on, 1-week off schedule, administered weekly at 1,000 mg/m2.A detailed medical history with physical examination and quality of life assessment will be performed at 4 months, 6 months, 9 months and 1 year. A follow-up visit at 4 weeks is optional and may be done by patient's Medical Oncologist. Scans may be done at 4-6 week visit if patient is being re-evaluated for resection.
In years 2-5 the follow up interval will be every 3-6 months, as determined by the investigator at each participating institution. Follow up intervals may also be more frequent as indicated clinically. A complete blood count (CBC), comprehensive chemistry panel, tumor marker studies, and quality of life assessment will be performed at each follow-up interval until death. As permitted by each participating institution, separate samples of blood will be drawn and retained for research efforts to develop novel serum biomarkers.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||59 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Multi-Institutional Study to Evaluate the Efficacy of Gemcitabine and Fractionated Stereotactic Radiotherapy for Unresectable Pancreatic Adenocarcinoma|
|Study Start Date :||October 2009|
|Actual Primary Completion Date :||October 2013|
|Actual Study Completion Date :||October 2015|
Experimental: SBRT and Gemzar
Before stereotactic Body Radiotherapy (SBRT) 3-5 gold fiducials are placed by endoscopic ultrasound or CT guidance. A simulation FDG-PET/CT (Fludeoxyglucose (18F) - Positron emission tomography/Computerized tomography) scan will be used for treatment planning purposes (standard free-breathing CT and respiratory-correlated 4-D (4 dimensional) pancreatic protocol CT). Patients are treated by either respiratory gated (Trilogy, Elekta, Novalis) or by respiratory tracking (CyberKnife). SBRT is delivered in 5 fractions of 6.6 Gy by LINAC-based or CyberKnife based radiotherapy over a five-day period. Gemcitabine, cycles should resume/start up to 4 weeks following SBRT on a 3-week on, 1-week off schedule. Initial follow up is at 4, 6, 9 and 12 months and then for years 2-5 is every 3-6 months.
Device: CyberKnife based stereotactic radiotherapy
Other Names:Drug: Gemcitabine
Treatment calculated per the needs of each patient and given at the instruction of the investigator; iv (intravenous).
Other Name: GemzarDrug: Fludeoxyglucose (18F) (FDG)
FDG-PET/CT scan is used in treatment planning. Treatment with 18F-FDG is calculated per the needs of each patient and given at the instruction of the investigator; iv
- To Determine the Rate of (Grade 2 or Greater) Gastrointestinal Toxicity Attributable to Gemcitabine and Fractionated SBRT at One Year. [ Time Frame: One year. ]Grade 2 or greater late gastritis, fistula, enteritis, or ulcer or late grade 3-4 gastrointestinal toxicity at one year.
- Evaluate Acute Gastrointestinal Toxicity up to 3 Months of Treatment. [ Time Frame: Within 3 months of treatment. ]Acute grade 2 or greater gastritis, fistula, enteritis, or ulcer or any other grade 3-4 gastrointestinal toxicity within 3 months of treatment.
- To Evaluate Progression Free Survival Following Gemcitabine and SBRT for up to 5 Years of Follow up . [ Time Frame: Up to 5 years of follow up. ]
Time to progression free survival is measured from start of SBRT treatment until first progression event or death, which ever comes first. If the patient did not have an event, then the patient was censored at the last follow up.
The analysis was a Kaplan-Meier curve and the outcome was the median time to progression free survival.
- To Determine the Overall Survival in Pancreatic Cancer Patients Treated With Gemcitabine and SBRT for up to 5 Years of Follow up. [ Time Frame: Up to 5 years of follow up. ]Time to death was measured from start of treatment to until death. If death was not observed, the patient was censored at last follow up.
- Proportion of Participants Achieving Freedom From Local Progression (FFLP) in Patients Treated With Gemcitabine Followed by Fractionated Stereotactic Body Radiotherapy (SBRT) for up to 5 Years of Follow up. [ Time Frame: Up to 5 years of follow up. ]
Freedom from local progression is defined as the time from start of SBRT treatment to local progression, with death as a competing risk. If the patient neither died nor experienced local progression, then patient was censored at last follow up.
The data was analyzed in a competing risk model and the outcome reported was the 1 year cumulative incidence rate.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01146054
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21231|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Albert Koong||Stanford University|