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 is a specialized radiation therapy that sends x-rays directly to the tumor using smaller doses over several days and may 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, by stopping them from dividing, or by stopping them from spreading. 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.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01918644.
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. Explore the use of MRI and positron emission tomography (PET) in evaluating for radiation complications, for example in the adjacent bowel.
VII. To describe in the biopsy and/or the surgical specimen, expression of following markers: SPARC (secreted protein acidic and rich in cysteine) expression; distribution of pancreatic stellate cells (PSC); distribution of CD4+/CD8+ T cell, CD56+ natural killer (NK) cells; other molecular and inflammatory cellular markers may be explored.
VIII. To describe changes induced by neoadjuvant therapy by comparison of expression of these markers between the biopsy and the surgical specimen.
IX. 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.
Patients 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. Patients then undergo definitive surgery after a minimum of 2 weeks from the completion of SBRT.
After completion of study treatment, patients are followed up at 1 month and 3 months, every 3 months for 1 year, and then every 6 months for 2 years.
Lead OrganizationUniversity of Wisconsin Carbone Cancer Center - University Hospital
Principal InvestigatorMichael F. Bassetti