Trial Outcomes & Findings for Phase II Gemcitabine + Fractionated Stereotactic Radiotherapy for Unresectable Pancreatic Adenocarcinoma (NCT NCT01146054)
NCT ID: NCT01146054
Last Updated: 2017-12-19
Results Overview
Grade 2 or greater late gastritis, fistula, enteritis, or ulcer or late grade 3-4 gastrointestinal toxicity at one year.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
59 participants
Primary outcome timeframe
One year.
Results posted on
2017-12-19
Participant Flow
Patients were recruited during new patient clinical visits between 10/22/2009 - 08/14/2013 at Stanford University, Johns Hopkins University and Memorial Sloan-Kettering Cancer Center. Study details were explained by the physician and consent was obtained by the physician or study coordinator according to good clinical practices.
Participant milestones
| Measure |
SBRT and Gemzar
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 starts within 4 weeks of 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.
Fludeoxyglucose (18F): 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
|
|---|---|
|
Overall Study
STARTED
|
59
|
|
Overall Study
COMPLETED
|
49
|
|
Overall Study
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
SBRT and Gemzar
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 starts within 4 weeks of 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.
Fludeoxyglucose (18F): 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
|
|---|---|
|
Overall Study
Did not meet dose constraints for SBRT
|
5
|
|
Overall Study
Rapid tumor progression
|
2
|
|
Overall Study
Other illness precluded treatment
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
Baseline Characteristics
Phase II Gemcitabine + Fractionated Stereotactic Radiotherapy for Unresectable Pancreatic Adenocarcinoma
Baseline characteristics by cohort
| Measure |
SBRT and Gemzar
n=49 Participants
Before stereotactic Body Radiotherapy (SBRT) 3-5 gold fiducials are placed by endoscopic ultrasound or CT guidance. A simulation FDG-PET/CT (Fludeoxyglucose (18F)) scan will be used for treatment planning purposes (standard free-breathing CT and respiratory-correlated 4-D 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
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
33 Participants
n=93 Participants
|
|
Age, Continuous
|
67 Years
n=93 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
49 participants
n=93 Participants
|
|
Baseline Cancer Antigen 19-9 (CA19-9)
CA 19-9 < 90 U/mL
|
18 Participants
n=93 Participants
|
|
Baseline Cancer Antigen 19-9 (CA19-9)
CA 19-9 >= 90 U/mL
|
27 Participants
n=93 Participants
|
|
Eastern Cooperative Oncology Group performance status (ECOG PS)
ECOG 0
|
21 Participants
n=93 Participants
|
|
Eastern Cooperative Oncology Group performance status (ECOG PS)
ECOG 1
|
28 Participants
n=93 Participants
|
|
Treating Institutions
Johns Hopkins University
|
32 Participants
n=93 Participants
|
|
Treating Institutions
Memorial Sloan-Kettering Cancer Center
|
3 Participants
n=93 Participants
|
|
Treating Institutions
Stanford University
|
14 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: One year.Population: The whole cohort was analyzed.
Grade 2 or greater late gastritis, fistula, enteritis, or ulcer or late grade 3-4 gastrointestinal toxicity at one year.
Outcome measures
| Measure |
SBRT and Gemzar
n=49 Participants
3-5 gold fiducials are placed by endoscopic ultrasound or CT guidance. A simulation FDG-PET/CT (Fludeoxyglucose (18F)) scan will be used for treatment planning purposes (standard free-breathing CT and respiratory-correlated 4-D 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 starts within 4 weeks of 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.
Fludeoxyglucose (18F): 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.
|
5 Number of toxicities.
|
SECONDARY outcome
Timeframe: Within 3 months of treatment.Population: Whole cohort.
Acute grade 2 or greater gastritis, fistula, enteritis, or ulcer or any other grade 3-4 gastrointestinal toxicity within 3 months of treatment.
Outcome measures
| Measure |
SBRT and Gemzar
n=49 Participants
3-5 gold fiducials are placed by endoscopic ultrasound or CT guidance. A simulation FDG-PET/CT (Fludeoxyglucose (18F)) scan will be used for treatment planning purposes (standard free-breathing CT and respiratory-correlated 4-D 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 starts within 4 weeks of 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.
Fludeoxyglucose (18F): 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
|
|---|---|
|
Evaluate Acute Gastrointestinal Toxicity up to 3 Months of Treatment.
|
14 Number of toxicities.
|
SECONDARY outcome
Timeframe: Up to 5 years of follow up.Population: The whole cohort.
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.
Outcome measures
| Measure |
SBRT and Gemzar
n=49 Participants
3-5 gold fiducials are placed by endoscopic ultrasound or CT guidance. A simulation FDG-PET/CT (Fludeoxyglucose (18F)) scan will be used for treatment planning purposes (standard free-breathing CT and respiratory-correlated 4-D 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 starts within 4 weeks of 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.
Fludeoxyglucose (18F): 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 Evaluate Progression Free Survival Following Gemcitabine and SBRT for up to 5 Years of Follow up .
|
7.8 Months
Interval 5.8 to 10.2
|
SECONDARY outcome
Timeframe: Up to 5 years of follow up.Population: The entire cohort.
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.
Outcome measures
| Measure |
SBRT and Gemzar
n=49 Participants
3-5 gold fiducials are placed by endoscopic ultrasound or CT guidance. A simulation FDG-PET/CT (Fludeoxyglucose (18F)) scan will be used for treatment planning purposes (standard free-breathing CT and respiratory-correlated 4-D 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 starts within 4 weeks of 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.
Fludeoxyglucose (18F): 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 Overall Survival in Pancreatic Cancer Patients Treated With Gemcitabine and SBRT for up to 5 Years of Follow up.
|
13.9 Months
Interval 10.2 to 16.7
|
SECONDARY outcome
Timeframe: 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.
Outcome measures
| Measure |
SBRT and Gemzar
n=49 Participants
3-5 gold fiducials are placed by endoscopic ultrasound or CT guidance. A simulation FDG-PET/CT (Fludeoxyglucose (18F)) scan will be used for treatment planning purposes (standard free-breathing CT and respiratory-correlated 4-D 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 starts within 4 weeks of 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.
Fludeoxyglucose (18F): 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
|
|---|---|
|
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.
|
0.78 Proportion of participants with FFLP
Interval 0.6 to 0.89
|
Adverse Events
SBRT and Gemzar
Serious events: 6 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
SBRT and Gemzar
n=49 participants at risk
3-5 gold fiducials are placed by endoscopic ultrasound or CT guidance. A simulation FDG-PET/CT (Fludeoxyglucose (18F)) scan will be used for treatment planning purposes (standard free-breathing CT and respiratory-correlated 4-D 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 starts within 4 weeks of 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.
Fludeoxyglucose (18F): 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
|
|---|---|
|
Gastrointestinal disorders
Duodenal Ulcer
|
2.0%
1/49 • Number of events 1 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Metabolism and nutrition disorders
Dehydration
|
2.0%
1/49 • Number of events 1 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Infections and infestations
Sepsis
|
2.0%
1/49 • Number of events 1 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Gastrointestinal disorders
Duodenal Fistula
|
2.0%
1/49 • Number of events 1 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Gastrointestinal disorders
Duodenal hemorrhage
|
2.0%
1/49 • Number of events 1 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
Other adverse events
| Measure |
SBRT and Gemzar
n=49 participants at risk
3-5 gold fiducials are placed by endoscopic ultrasound or CT guidance. A simulation FDG-PET/CT (Fludeoxyglucose (18F)) scan will be used for treatment planning purposes (standard free-breathing CT and respiratory-correlated 4-D 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 starts within 4 weeks of 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.
Fludeoxyglucose (18F): 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
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
24.5%
12/49 • Number of events 12 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Metabolism and nutrition disorders
Anorexia
|
26.5%
13/49 • Number of events 13 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Gastrointestinal disorders
Constipation
|
6.1%
3/49 • Number of events 3 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Gastrointestinal disorders
Dyspepsia
|
8.2%
4/49 • Number of events 4 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
General disorders
Fatigue
|
26.5%
13/49 • Number of events 13 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Gastrointestinal disorders
Nausea
|
12.2%
6/49 • Number of events 6 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Blood and lymphatic system disorders
Anemia
|
28.6%
14/49 • Number of events 14 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Investigations
Lymphocyte count decreased
|
28.6%
14/49 • Number of events 14 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
|
Investigations
Platelet Count Decreased
|
10.2%
5/49 • Number of events 5 • Adverse events were collected from start of treatment to end of follow up (5 years).
|
Additional Information
Albert C. Koong, M.D., Ph.D., Sue and Bob McCollum Professor, Associate Chair of Radiation Onocology
Stanford University Comprehensive Cancer Center
Phone: 650-498-7703
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place