Stereotactic Body Radiation Therapy and Capecitabine Before Surgery in Treating Patients With Pancreatic Cancer That Can be Removed by Surgery
Conditions
Stage IA Pancreatic Cancer - Stage IB Pancreatic Cancer - Stage IIA Pancreatic Cancer - Stage IIB Pancreatic Cancer
Conditions: official terms
Pancreatic Neoplasms
Study Type
Interventional
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: stereotactic body radiation therapy Type: Radiation
Name: capecitabine Type: Drug
Name: therapeutic conventional surgery Type: Procedure
Name: magnetic resonance imaging Type: Procedure
Name: laboratory biomarker analysis Type: Other
Overall Status
Recruiting
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. 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.

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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 19 Years
Gender: Both
Criteria: 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) 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) =< 2.5 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

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

- Helicobacter pylori (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 therapy for pancreatic cancer, any prior radiation therapy to the upper abdomen, 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
Location
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States
Status: Recruiting
Contact: Cancer Connect - 800-622-8922 - cancerconnect@uwcarbone.wisc.edu
Start Date
August 2013
Completion Date
July 2016
Sponsors
University of Wisconsin, Madison
Source
University of Wisconsin, Madison
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page