Clinical trial NCT02780648: Respiratory-gated Stereotactic Body Radiation Therapy for Adenocarcinoma of the Pancreas or Periampullary Region
Official title: Pilot Study of Respiratory-gated Stereotactic Body Radiation Therapy for Borderline Resectable, Unresectable, or Recurrent/residual Adenocarcinoma of the Pancreas or Periampullary Region
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pancreatic Neoplasms
Keywords: stereotactic radiotherapy
pancreatic adenocarcinoma
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2016-05-23
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Acute toxicity rates of grade 3 gastrointestinal and hematologic toxicities (as raw percentage)
timeFrame: 3 months after treatment
Secondary outcomes:
measure: Late toxicity rates of grade 2 gastritis, enteritis, fistula, and ulcer, or any other grade 3 or greater gastrointestinal (as raw percentage)
timeFrame: 6 months, 9 months, and 1 year after treatment
measure: Overall survival rates
timeFrame: 1 year after treatment
measure: Progression-free survival rates
timeFrame: 1 year after treatment
measure: Metastasis-free survival rates
timeFrame: 1 year after treatment
measure: Patient self-report of pain control
timeFrame: 1 month and 3 months after treatment
measure: Patient self-report of quality of life
timeFrame: 1 month, 3 months, 6 months, 9 months, and 1 year after treatment
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Health Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Health Melvin and Bren Simon Cancer Center
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine, Indiana University Simon Cancer Center
name: Robert Miller, MD
role: PRINCIPAL_INVESTIGATOR
References: