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.
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. III. To estimate the pathological response rates. IV. To estimate the rates of resection with negative margins. V. To estimate the recurrence free survival (RFS). VI. To estimate the overall survival (OS). TERTIARY OBJECTIVES (OPTIONAL): I. To define tumor volume (TV), dynamic contrast enhancement (DCE) pattern and mean apparent diffusion coefficient (ADC) measurements in diffusion-weighted magnetic resonance (MR) imaging (DWI) in patients with resectable pancreatic cancer undergoing neoadjuvant SBRT and concomitant chemotherapy (ChT). II. To correlate TV, DCE and ADC measurements at baseline magnetic resonance imaging (MRI) versus final pathological response. III. To correlate TV, DCE and ADC changes from baseline in MRI done three weeks post-SBRT versus final pathological response. IV. To predict surgical margin status using MRI done at baseline and at three weeks post-SBRT. V. To correlate TV, DCE and ADC changes from baseline in MRI done post-3rd fraction at baseline versus final pathological response. VI. To describe in the biopsy and/ or the surgical specimen, expression of following markers: secreted protein acidic and rich in cysteine (SPARC) expression; distribution of pancreatic stellate cells (PSC); distribution of cluster of differentiation (CD)4+/ CD8+ T cell, CD56+ natural killer (NK) cells; other molecular and inflammatory cellular markers may be explored. VII. To describe changes induced by neoadjuvant therapy by comparison of expression of these markers between the biopsy and the surgical specimen. VIII. To compare baseline and/ or post-treatment expression with treatment response, toxicity and clinical survival outcome. OUTLINE: This is a dose-escalation study of SBRT. Participants undergo SBRT every other day over 2 weeks for a total of 5 fractions and receive capecitabine orally (PO) every 12 hours 5 days a week for 2 weeks. Participants then undergo definitive surgery after a minimum of 2 weeks from the completion of SBRT. After completion of study treatment, participants are followed up at 1 month and 3 months, every 3 months for 1 year, and then every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
21
Undergo SBRT
Given PO
Undergo definitive surgery
Optional correlative studies
Optional correlative studies
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States
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
The number and percent of patients reporting adverse events (all, severe or worse, serious and related) will be quantified for each dose level.
Time frame: Up to 90 days from the start of SBRT and capecitabine
Incidence of 30-day post-operative complications
Will be expressed as a percentage.
Time frame: 30 days
Radiological response per Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric measurements
Will be expressed as a percentage.
Time frame: Up to 3 years
Pathological response, graded based on the College of American Pathologists (CAP) and Ishikawa, Evans, and Chun grading systems
Will be expressed as a percentage.
Time frame: Up to 3 years
Incidence of margin-negative resection, defined as the absence of viable tumor cells at the inked surgical margin
Will be expressed as a percentage.
Time frame: Up to 3 years
Loco-regional recurrence free survival, defined with follow-up radiological assessment
Kaplan-Meier estimates will be calculated. Log-rank test and Cox regression analysis will be used for univariate and multivariate analyses, respectively. Chi square and regression analysis will be performed to test association of categorical variables with treatment response.
Time frame: From the point of start of SBRT to the point of recurrence or death, assessed up to 3 years
OS
Kaplan-Meier estimates will be calculated. Log-rank test and Cox regression analysis will be used for univariate and multivariate analyses, respectively. Chi square and regression analysis will be performed to test association of categorical variables with treatment response.
Time frame: From the point of start of SBRT to the time of death or last follow-up if alive, assessed up to 3 years
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