A Phase Ia-Ib Dose-escalation Study Evaluating Safety and Efficacy of Neoadjuvant Stereotactic Body Radiotherapy (SBRT) With Concomitant Capecitabine Chemotherapy for Resectable Carcinoma of Exocrine Pancreas.
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 21
- Locations
- 1
- Primary Endpoint
- Incidence of dose-limiting toxicity defined as any grade 3-4 non-hematologic toxicity or grade 5 toxicity attributable to combination chemo-radiotherapy per the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Study Overview
Brief Summary
This phase I trial studies the side effects and best dose of stereotactic body radiation therapy when given together with capecitabine before surgery in treating patients with pancreatic cancer that can be removed by surgery. Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving stereotactic body radiation therapy and capecitabine before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the recommended-phase-II-dose (RPTD) of stereotactic body radiation therapy (SBRT) at an escalating dose schedule when combined with standard-dose capecitabine as neoadjuvant therapy for resectable carcinoma of exocrine pancreas.
SECONDARY OBJECTIVES:
I. To estimate the incidence of overall 30-day post-operative complications.
II. To estimate the radiological response rates.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 19 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histologically or cytologically confirmed carcinoma of exocrine pancreatic head amenable to oncological surgical resection per findings on a pancreatic-specific computed tomography (CT) or MRI scan. Tumors of the body that allow a surgical approach similar to pancreatic head tumors are acceptable.
- •Must be deemed a surgical candidate by the surgical oncology service.
- •Eastern Cooperative Oncology Group (ECOG) performance score of =< 2
- •Signed informed consent document(s)
- •Patients with no evidence of regional or distant metastatic disease based on CT scan of the chest/ abdomen/pelvis.
- •Absolute neutrophil count (ANC) >= 1,500 cells/mm3
- •Platelet count >= 100,000 cells/mm3
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 times the upper limit of normal
- •Total bilirubin =< 3 times the upper limit of normal if patient had recent biliary stenting, total bilirubin =< 1.5 times the upper limit of normal if no biliary stenting was done
- •Serum creatinine within normal range with a creatinine clearance >= 30 ml/min
- •Neoadjuvant chemotherapy will be permitted prior to the initiation of SBRT radiation therapy on this clinical trial. There must be a minimum of 2 weeks between the completion of any neoadjuvant chemotherapy and the beginning of SBRT radiation therapy. Furthermore, restaging must be done prior to registration to ensure that patients remain resectable.
Exclusion Criteria
- •Patients with primary ampullary, biliary or duodenal cancer would be excluded
- •Patients with tumors primarily of the body or tail of the pancreas requiring a distal pancreaticoduodenectomy would be excluded
- •(H/ o) Crohn's disease/ ulcerative colitis/ scleroderma
- •History of prior allergic reactions attributed to compounds of similar chemical or biologic composition as capecitabine
- •History of prior allergic reactions attributed to compounds of CT/ MRI contrast that cannot be managed with appropriate pre-medication prophylaxis and thereby preclude use of baseline/ follow-up or radiation planning imaging
- •Any prior external beam radiation will be evaluated to determine radiation field overlaps and appropriateness of protocol radiation, any invasive cancer in the last 5 years (except for a diagnosis of low-risk prostate cancer, treated non-melanoma/melanoma skin cancer, appropriately treated ductal carcinoma in situ or early stage invasive carcinoma of breast and appropriately treated in-situ/early stage cervical/endometrial cancer)
- •Pregnant or nursing women; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the point of study entry and for the duration of all active treatments; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Treatment with a non-approved or investigational drug within 28 days of study treatment
- •History of having MRI non-compatible metal (injury- or treatment-related) in the body will be an exclusion criteria specific to the MRI sub-study
- •Considering the small size of the PET/MR scanner bore, subjects with known severe claustrophobia or with body habitus not compatible with the bore (>300lbs, BMI>40) may also have to be excluded.
- •Subjects unable to maintain blood glucose less than 200mg/dl may not be suitable for the PET/MRI substudy.
Arms & Interventions
Treatment (SBRT, capecitabine, and surgery)
Patients undergo SBRT every other day over 2 weeks for a total of 5 fractions and receive capecitabine PO every 12 hours 5 days a week for 2 weeks. Patients then undergo definitive surgery after a minimum of 2 weeks from the completion of SBRT.
Intervention: stereotactic body radiation therapy (Radiation)
Treatment (SBRT, capecitabine, and surgery)
Patients undergo SBRT every other day over 2 weeks for a total of 5 fractions and receive capecitabine PO every 12 hours 5 days a week for 2 weeks. Patients then undergo definitive surgery after a minimum of 2 weeks from the completion of SBRT.
Intervention: capecitabine (Drug)
Treatment (SBRT, capecitabine, and surgery)
Patients undergo SBRT every other day over 2 weeks for a total of 5 fractions and receive capecitabine PO every 12 hours 5 days a week for 2 weeks. Patients then undergo definitive surgery after a minimum of 2 weeks from the completion of SBRT.
Intervention: therapeutic conventional surgery (Procedure)
Treatment (SBRT, capecitabine, and surgery)
Patients undergo SBRT every other day over 2 weeks for a total of 5 fractions and receive capecitabine PO every 12 hours 5 days a week for 2 weeks. Patients then undergo definitive surgery after a minimum of 2 weeks from the completion of SBRT.
Intervention: magnetic resonance imaging (Procedure)
Treatment (SBRT, capecitabine, and surgery)
Patients undergo SBRT every other day over 2 weeks for a total of 5 fractions and receive capecitabine PO every 12 hours 5 days a week for 2 weeks. Patients then undergo definitive surgery after a minimum of 2 weeks from the completion of SBRT.
Intervention: laboratory biomarker analysis (Other)
Outcomes
Primary Outcomes
Incidence of dose-limiting toxicity defined as any grade 3-4 non-hematologic toxicity or grade 5 toxicity attributable to combination chemo-radiotherapy per the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame: Up to 90 days from the start of SBRT and capecitabine
The number and percent of patients reporting adverse events (all, severe or worse, serious and related) will be quantified for each dose level.
Secondary Outcomes
- Pathological response, graded based on the College of American Pathologists (CAP) and Ishikawa, Evans, and Chun grading systems(Up to 3 years)
- Radiological response per Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric measurements(Up to 3 years)
- Incidence of 30-day post-operative complications(30 days)
- Incidence of margin-negative resection, defined as the absence of viable tumor cells at the inked surgical margin(Up to 3 years)
- Loco-regional recurrence free survival, defined with follow-up radiological assessment(From the point of start of SBRT to the point of recurrence or death, assessed up to 3 years)
- OS(From the point of start of SBRT to the time of death or last follow-up if alive, assessed up to 3 years)