Trial Outcomes & Findings for A Dose Escalation Trial of SBRT After Induction Chemotherapy for Locally Advanced Pancreatic Cancer (NCT NCT02873598)

Last Updated: 2022-12-19

Results Overview

This will be accomplished by the standard 3+3 dose escalation design. Dose limiting toxicities (DLT) are defined by ≥ Grade 3 treatment-related GI toxicity within 3 months of SBRT. These include: (1) Bowel (includes bowel perforation, obstruction, or hemorrhage) and (2) Stomach (bleeding ulcer, perforation) as determined by imaging or endoscopic evaluation.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

Up to 3 months

Results posted on

2022-12-19

Participant Flow

Participant milestones

Participant milestones
Measure	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose 1 SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 1 - 9 Gy x 3 fractions. FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose 2 SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 2 - 10 Gy x 3 fractions. FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose 3 SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 3 - 11 Gy x 3 fractions. FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
Overall Study STARTED	5	5	4
Overall Study COMPLETED	5	5	4
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Dose Escalation Trial of SBRT After Induction Chemotherapy for Locally Advanced Pancreatic Cancer

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: Up to 3 months

Outcome measures

Outcome measures
Measure	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT n=14 Participants SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
The Maximum Tolerated Dose (MTD) of Stereotactic Body Radiotherapy (SBRT) in Locally Advanced Pancreatic Cancer (LAPC) Patients Who Have Not Developed Distant Progression After Induction Chemotherapies.	33 grey

SECONDARY outcome

Timeframe: Up to 5 years

Local control (LC) will be measured from completion of SBRT to the time of identification of any local progression by imaging or surgical exploration. The pattern of patients experiencing local, distant or local with distant failure will be estimated using competing risks method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years

Progression free survival (PFS) will be measured from completion of SBRT to the time of tumor progression or death due to any cause. PFS will be estimated using the method of Kaplan and Meier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 5 years

Overall survival (OS) will be measured from completion of SBRT until death due to any cause. OS will be estimated using the method of Kaplan and Meier.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after SBRT

Investigators will measure changes in the perfusion/permeability related parameters of peripancreatic small intestine before, during and after SBRT for patients using pCT and correlating these changes with the development of gastrointestinal toxicity such as duodenal ulcers, strictures, or enteritis. Patients will undergo baseline, post-first-fraction SBRT and post-treatment CT scans.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks after SBRT

Investigators will measure changes in diffusion and perfusion/permeability by using perfusion CT derived parameters that can predict treatment response and to assess any correlation between these perfusion CT derived parameters and local control and progression-free survival

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months after SBRT

The primary objective of the QOL study is to document the patient's experience of treatment for locally advanced pancreatic cancer by examining global QOL, physical symptoms, physical functioning and emotional well-being at baseline, during treatment, and after treatment. QOL measures including EORTC-QLQ-C30 questionnaire and the Pancreatic Cancer subscale (EORTC-PAN26) will be assessed 14 days prior to SBRT (Time 0), 10-12 weeks after SBRT (Time 1), and 6 months after SBRT (Time 2). The primary QOL endpoints include the EORTC global QOL, physical symptoms, physical functioning and emotional well-being.

Outcome measures

Outcome data not reported

Adverse Events

FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 1

Serious events: 0 serious events

Other events: 4 other events

Deaths: 4 deaths

FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 3 deaths

FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 3

Serious events: 1 serious events

Other events: 4 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 1 n=5 participants at risk SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 1 - 9 Gy x 3 fractions FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 2 n=5 participants at risk SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 2 - 10 Gy x 3 fractions FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 3 n=4 participants at risk SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 3 - 1Gy x 3 fractions FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
Blood and lymphatic system disorders Anemia	0.00% 0/5 • 24 months	20.0% 1/5 • Number of events 1 • 24 months	0.00% 0/4 • 24 months
General disorders Anorexia	0.00% 0/5 • 24 months	0.00% 0/5 • 24 months	25.0% 1/4 • Number of events 1 • 24 months
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	0.00% 0/5 • 24 months	0.00% 0/5 • 24 months	25.0% 1/4 • Number of events 1 • 24 months

Other adverse events

Other adverse events
Measure	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 1 n=5 participants at risk SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 1 - 9 Gy x 3 fractions FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 2 n=5 participants at risk SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 2 - 10 Gy x 3 fractions FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 3 n=4 participants at risk SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 3 - 1Gy x 3 fractions FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.
Gastrointestinal disorders diarrhea	0.00% 0/5 • 24 months	20.0% 1/5 • Number of events 1 • 24 months	25.0% 1/4 • Number of events 2 • 24 months
Gastrointestinal disorders dyspepsia	0.00% 0/5 • 24 months	20.0% 1/5 • Number of events 1 • 24 months	0.00% 0/4 • 24 months
Gastrointestinal disorders Abdominal Pain	20.0% 1/5 • Number of events 1 • 24 months	0.00% 0/5 • 24 months	0.00% 0/4 • 24 months
General disorders Anorexia	20.0% 1/5 • Number of events 1 • 24 months	0.00% 0/5 • 24 months	0.00% 0/4 • 24 months
Gastrointestinal disorders Bloating	20.0% 1/5 • Number of events 1 • 24 months	0.00% 0/5 • 24 months	25.0% 1/4 • Number of events 1 • 24 months
Gastrointestinal disorders esophagitis	0.00% 0/5 • 24 months	20.0% 1/5 • Number of events 1 • 24 months	0.00% 0/4 • 24 months
General disorders fatigue	40.0% 2/5 • Number of events 3 • 24 months	20.0% 1/5 • Number of events 3 • 24 months	25.0% 1/4 • Number of events 1 • 24 months
General disorders flank pain	20.0% 1/5 • Number of events 1 • 24 months	0.00% 0/5 • 24 months	25.0% 1/4 • Number of events 1 • 24 months
Gastrointestinal disorders gastroinstestinal disorder	40.0% 2/5 • Number of events 2 • 24 months	20.0% 1/5 • Number of events 1 • 24 months	0.00% 0/4 • 24 months
Gastrointestinal disorders nausea	40.0% 2/5 • Number of events 2 • 24 months	20.0% 1/5 • Number of events 2 • 24 months	50.0% 2/4 • Number of events 4 • 24 months
General disorders non-cardiac chest pain	0.00% 0/5 • 24 months	0.00% 0/5 • 24 months	25.0% 1/4 • Number of events 1 • 24 months
Respiratory, thoracic and mediastinal disorders pleural effusion	0.00% 0/5 • 24 months	0.00% 0/5 • 24 months	25.0% 1/4 • Number of events 1 • 24 months
Gastrointestinal disorders vomitting	0.00% 0/5 • 24 months	20.0% 1/5 • Number of events 1 • 24 months	25.0% 1/4 • Number of events 1 • 24 months
Gastrointestinal disorders weight loss	0.00% 0/5 • 24 months	40.0% 2/5 • Number of events 3 • 24 months	0.00% 0/4 • 24 months

Additional Information

Dr. Sana Karam

University of Colorado Cancer Center

Phone: 7208480141

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 1 n=5 Participants SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 1 - 9 Gy x 3 fractions. FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 2 n=5 Participants SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 2 - 10 Gy x 3 fractions. FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.	FOLFIRINOX or Gemcitabine/Abraxane Followed by SBRT Dose Level 3 n=4 Participants SBRT will be administered in 3 fractions, every other day, on an outpatient basis, following chemotherapy with either FOLFIRINOX or gemcitabine/abraxane. Dose level 3 - 11 Gy x 3 fractions. FOLFIRINOX or gemcitabine/abraxane: Patients will have received induction chemotherapy for 3+ months with either FOLFIRINOX or gemcitabine/abraxane with at least stable disease. SBRT: After completion of induction chemotherapy, stereotactic body radiation therapy (SBRT) will be administered in 3 fractions, every other day, on an outpatient basis. Dose escalation will start with dose level 1 (9 Gy x 3 fractions) and increase by 1 Gy per fraction at each dose level, dose level 2 will be 10 Gy x 3 fractions and dose level 3 will be 11 Gy x 3 fractions.	Total n=14 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Age, Continuous	67 years n=5 Participants	68 years n=7 Participants	55 years n=5 Participants	67 years n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	14 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	5 participants n=5 Participants	5 participants n=7 Participants	4 participants n=5 Participants	14 participants n=4 Participants