Respiratory-gated Stereotactic Body Radiation Therapy for Adenocarcinoma of the Pancreas or Periampullary Region

Pilot Study of Respiratory-gated Stereotactic Body Radiation Therapy for Borderline Resectable, Unresectable, or Recurrent/Residual Adenocarcinoma of the Pancreas or Periampullary Region

This is a single center, single arm unblinded prospective study of the safety of pancreatic stereotactic body radiation therapy (SBRT) in patients with unresectable, borderline resectable, or recurrent pancreatic/periampullary cancers who have previously undergone treatment with chemotherapy, surgery, photodynamic therapy, conventionally fractionated radiation treatment, or any combination of these therapies.

Primary Objective

• To estimate rates of acute (within 3 months of treatment) grade 3 or greater gastrointestinal and hematologic toxicity in patients treated with Linac-based SBRT for pancreatic or periampullary cancers who have previously received other treatment.

Secondary Objectives

• To estimate rates of late (> 3 months after treatment) grade 2 gastritis, enteritis, fistula, and ulcer, or any other grade 3 or greater gastrointestinal toxicity in patients treated with Linac-based SBRT for pancreatic or periampullary cancers
• To estimate rates of local progression, overall survival, metastasis-free survival, and progression-free survival in patients with pancreatic or periampullary cancers treated with fractionated Linac-based SBRT.
• To evaluate the ability of Linac-based SBRT to provide pain control in patients with pain related to a pancreatic or periampullary tumor.
• To evaluate quality of life in patients undergoing treatment with Linac-based SBRT for pancreatic or periampullary cancers.

Study Overview

• Status: Completed
• Conditions: Pancreatic Neoplasms
• Intervention / Treatment: Radiation: Stereotactic Body Radiation

Detailed Description

Patients will receive 5 fractions of 5 gray (Gy) or 6.6 Gy delivered over a five-day period based on whether or not they have received prior radiation therapy to the pancreatic region. Treatment may be delivered over 2 weeks, provided that the patient receives at least 2 fractions per week. Initial patient positioning will be based on volumetric kV (cone-beam computerized tomography) imaging with shifts to bony anatomy as appropriate. Orthogonal kV/MV or kV/kV projection imaging will be used to verify the location of the fiducials prior to delivery of the first treatment beam. A secondary shift based on the location of fiducials may be utilized, as indicated by the position of the fiducials. For free-breathing treatments, kV fluoroscopic images should be obtained to confirm the anticipated position of these fiducials during the entire respiratory cycle. Active monitoring of treatment delivery accuracy will be accomplished using kV and/or MV projection imaging, either immediately before or during all (or a subset of) treatment fields. Patient-specific dosimetric quality assurance (QA) will be performed as per standard practice in the Department of Radiation Oncology, Indiana University School of Medicine.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Age >18 years.
• Karnofsky Performance Status >70%
• Histologically confirmed adenocarcinoma of the pancreas or ampulla of Vater; at least the majority of the histopathologic specimen must be identified as adenocarcinoma as opposed to another histologic subtype. In patients with a diagnosis of recurrent disease (based on radiographic progression and/or rising CA19-9 levels) and a history of a biopsy-proven adenocarcinoma of the pancreas or the ampulla of Vater, repeat biopsy of the recurrence site is not required for participation of the trial.
• Pancreatic or periampullary tumors must be less than 8.0 cm in greatest axial dimension at the time of treatment planning.
• Patients who have been treated with any combination of surgical resection and neoadjuvant/adjuvant conventional chemoradiation therapy for resectable disease or conventional chemoradiation as definitive treatment for unresectable or borderline resectable disease are eligible for the study, provided that at least 180 days have elapsed since completing any previous radiation treatment. Patients who have been receiving continued chemotherapy following their initial radiation treatment are eligible regardless of when the most recent chemotherapy was received. Those patients who have received prior radiation therapy will constitute Cohort A and will receive stereotactic body radiation (SBRT) as 5 gray (Gy) x 5.
• Patients who have not previously undergone radiation therapy can have a history of treatment with either chemotherapy (for unresectable/borderline resectable disease) or any combination of surgery and chemotherapy (for resectable disease). Patients with no history of prior radiation treatment will constitute Cohort B and will receive SBRT as 6.6 Gy x 5. Please note that patients must have received at least two cycles of chemotherapy (with selection of drugs at the discretion of the treating oncologist) before SBRT treatment on protocol.

• Acceptable organ and marrow function as defined below (within 2 weeks prior to radiotherapy):

  • Leukocytes >3,000/μL
  • Absolute neutrophil count >1,500μL
  • Platelets >100,000/μL
  • Total Bilirubin ≤1.5x institutional upper limit of normal
  • Aspartate transaminase (AST(SGOT))/Alanine transaminase (ALT(SGPT)) <2.5x institutional upper limit of normal
  • Creatinine ≤ institutional upper limit of normal OR creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
• Ability to understand and the willingness to sign a written informed consent document.
• Life expectancy > 3 months.
• Radio-opaque markers must be present within the tumor bed. In patients who have undergone surgical resection, radio-opaque surgical clips within the tumor bed can be used as fiducials. Patients without surgical clips in the tumor bed must be able to have fiducials placed endoscopically, laparoscopically, or through a CT- or ultrasound-guided technique. If not, the tumor must be posterior and adjacent to the aorta, and treatment will only be permitted at the discretion of the Principal Investigator.

Exclusion Criteria

• Age < 18 years.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (or infections requiring systemic antibiotic treatment), active upper GI ulceration or hemorrhage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Any concurrent malignancy other than non-melanoma skin cancer, non-invasive bladder cancer, early stage prostate cancer, or carcinoma in situ of the cervix. Patients with a previous non-pancreatic, non-periampullary malignancy without evidence of disease for > 5 years will be allowed to enter the trial.
• Pregnant and breastfeeding women are excluded as are women of child-bearing potential who are unwilling or unable to use an acceptable method of birth control (hormonal or barrier method of birth control; abstinence) to avoid pregnancy for the duration of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Women who are not post-menopausal (as defined in Appendix III) and have a positive urine or serum pregnancy test or refuse to take a pregnancy test.
• Patients with a life expectancy of < 3 months.
• Patients with metastatic disease.
• Patients with evidence of gross tumor invasion into the lumen of the stomach or small bowel are not eligible; if imaging suggests luminal invasion of tumor, this must be ruled out endoscopically before the patient can be enrolled on study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stereotactic Body Radiation; Patients will receive 5 fractions of 5 Gy or 6.6 Gy (dose depending upon whether or not they have received prior radiation therapy to the pancreatic region) delivered over a five-day period.	Radiation: Stereotactic Body Radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Toxicity Rates of Grade 3 or Greater Gastrointestinal and Hematologic Toxicities (as Raw Percentage)	Measures include the percentage of patients who experienced the toxicity with a grade of 3 or higher. Only those adverse events that were related to stereotactic body radiation therapy (SBRT) were considered. Patients were considered at risk for an adverse event if they started SBRT treatment. Toxicities per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.	Up to 90 days after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late, Treatment-related Toxicity Rates of Gastritis, Enteritis, Fistula, and Ulcer, or Any Other Gastrointestinal Toxicity (as Raw Percentage)	Measures include the percentage of patients who experienced the toxicity with a grade of 2 or higher. Only those adverse events that were related to stereotactic body radiation therapy (SBRT) were considered. Patients were considered at risk for an adverse event if they started SBRT treatment. Toxicities per Common Terminology Criteria for Adverse Events (CTCAE) 4.0.	90 or more days after treatment, up to 7 years
Overall Survival	This measure reports the overall survival probability from the Kaplan Meier method. The survival time was calculated from the date of treatment start to the date of death and patients who did not expire were censored at their last date known alive.	1 year after treatment
Progression-Free Survival	This measure represents the progression-free survival at one-year following treatment start. The survival time was calculated from the date of treatment start to the date of progression or death. Patients who did not experience progression were censored at their last known date alive.	1 year after treatment
Metastasis-Free Survival	This represents the metastasis-free survival at one-year following treatment start. The survival time was calculated from the date of treatment start to the date of metastasis or death. Patients who did not experience metastasis or death were censored at their last known date alive.	1 year after treatment
Wong-Baker FACES Pain Rating Score	Measured with the Wong-Baker FACES 0-10 scale where higher scores indicate more pain. Patients self-reported the score before (baseline), during (weeks 1 and 2), and after (1 and 3 months) treatment. Scores collected during treatment (weeks 1 and 2) were averaged to create a composite "during treatment" score. Similarly, scores collected after treatment (months 1 and 3) were averaged to create a composite "after treatment" score.	Baseline (before treatment), Week 1 (during treatment), Week 2 (during treatment), Month 1 (after treatment), and Month 3 (after treatment)
Quality of Life Scores - Global Health Status / Quality of Life	Patients completed the EORTC Quality of Life (QOL)-Q (QLQ-C30 Version 3) questionnaire before treatment, during treatment, and after treatment. The questionnaire includes 30 questions to assess the quality of life in cancer patients. The Global Health Status / Quality of Life composite score was calculated by combining the scores for questions 29 and 30 and calculating Score = {(RS -1) range}×100. Responses for questions 29 and 30 ranged from 1 to 7 with 1 indicating "Very Poor" and 7 indicating "Excellent". Higher scores indicate a better quality of life with a minimum composite score of 0 and a maximum composite score of 100. Scores collected during treatment (weeks 1 and 2) were averaged to create a composite "during treatment" score. Similarly, scores collected after treatment (months 1, 3, 6, 9, and 12) were averaged to create a composite "after treatment" score.	Baseline (before treatment), 1 week (during treatment), 2 weeks (during treatment), 1 month (after treatment), 3 months (after treatment), 6 months (after treatment), 9 months (after treatment), and 12 months (after treatment)
Quality of Life Scores - Functional Scales	Patients completed the EORTC Quality of Life (QOL)-Q (QLQ-C30 Version 3) questionnaire before treatment, during treatment, and after treatment. The questionnaire includes 30 questions to assess the quality of life in cancer patients. The Functional scales composite scores were calculated by combining the scores for the relevant questions and calculating Score = {1 - ((RS -1) / range)}×100. The response options for each question were "1-Not at all", "2-A little", "3-Quite a bit", and "4-Very Much". Higher scores indicate a high/healthy level of functioning with a minimum composite score of 0 and a maximum composite score of 100. In each category, scores collected during treatment (weeks 1 and 2) were averaged to create a composite "during treatment" score. Similarly, scores collected after treatment (months 1, 3, 6, 9, and 12) were averaged to create a composite "after treatment" score.	Baseline (before treatment), 1 week (during treatment), 2 weeks (during treatment), 1 month (after treatment), 3 months (after treatment), 6 months (after treatment), 9 months (after treatment), and 12 months (after treatment)
Quality of Life Scores - Symptom Scales	Patients completed the EORTC Quality of Life (QOL)-Q (QLQ-C30 Version 3) questionnaire before treatment, during treatment, and after treatment. The questionnaire includes 30 questions to assess the quality of life in cancer patients. The Symptom scales composite scores were calculated by combining the scores for the relevant questions and calculating Score = {(RS -1) range}×100. The response options for each question were "1-Not at all", "2-A little", "3-Quite a bit", and "4-Very Much". Higher scores indicate a high level of symptomatology / problems with a minimum composite score of 0 and a maximum composite score of 100. In each category, scores collected during treatment (weeks 1 and 2) were averaged to create a composite "during treatment" score. Similarly, scores collected after treatment (months 1, 3, 6, 9, and 12) were averaged to create a composite "after treatment" score.	Baseline (before treatment), 1 week (during treatment), 2 weeks (during treatment), 1 month (after treatment), 3 months (after treatment), 6 months (after treatment), 9 months (after treatment), and 12 months (after treatment)

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Robert Miller, MD, Indiana University School of Medicine, Indiana University Simon Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): December 17, 2019
• Study Completion (Actual): May 15, 2025

Study Registration Dates

• First Submitted: May 17, 2016
• First Submitted That Met QC Criteria: May 19, 2016
• First Posted (Estimated): May 23, 2016

Study Record Updates

• Last Update Posted (Estimated): November 3, 2025
• Last Update Submitted That Met QC Criteria: October 8, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: pancreatic adenocarcinoma; stereotactic radiotherapy
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: IUSCC-0565; 1601638414 (Other Identifier: Indiana University IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No