Neoadjuvant SBRT With Concomitant Capecitabine In Resectable Pancreatic Cancer

Study Overview

Neoadjuvant SBRT With Concomitant Capecitabine in Resectable Pancreatic Cancer

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.

Stage IA Pancreatic Cancer
Stage IB Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer

RADIATION: stereotactic body radiation therapy
DRUG: capecitabine
PROCEDURE: therapeutic conventional surgery
PROCEDURE: magnetic resonance imaging
OTHER: laboratory biomarker analysis

2017-1499
NCI-2013-01347 (REGISTRY Identifier) (REGISTRY: NCI Trial ID)
2013-0645 (OTHER Identifier) (OTHER: Institutional Review Board)
RO12210 (OTHER Identifier) (OTHER: University of Wisconsin Carbone Cancer Center)
A533300 (OTHER Identifier) (OTHER: UW Madison)
SMPH/HUMAN ONCOLOGY/HUMAN ONCO (OTHER Identifier) (OTHER: UW Madison)
Protocol Version 2/6/2018 (OTHER Identifier) (OTHER: UW Madison)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2013-08-05	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2022-05-31
First Submitted that Met QC Criteria 2013-08-05	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2022-06-01
First Posted (ACTUAL) 2013-08-08	Results First Posted N/A	Last Verified 2022-05

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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.	RADIATION: stereotactic body radiation therapy Undergo SBRT DRUG: capecitabine Given PO PROCEDURE: therapeutic conventional surgery Undergo definitive surgery PROCEDURE: magnetic resonance imaging Optional correlative studies OTHER: laboratory biomarker analysis Optional correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 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.

RADIATION: stereotactic body radiation therapy

Undergo SBRT

DRUG: capecitabine

Given PO

PROCEDURE: therapeutic conventional surgery

Undergo definitive surgery

PROCEDURE: magnetic resonance imaging

Optional correlative studies

OTHER: laboratory biomarker analysis

Optional correlative studies

Primary Outcome Measures	Measure Description	Time Frame
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.	Up to 90 days from the start of SBRT and capecitabine

Secondary Outcome Measures	Measure Description	Time Frame
Incidence of 30-day post-operative complications	Will be expressed as a percentage.	30 days
Radiological response per Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric measurements	Will be expressed as a percentage.	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.	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.	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.	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.	From the point of start of SBRT to the time of death or last follow-up if alive, assessed up to 3 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
19 Years

Accepts Healthy Volunteers:

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.

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Michael Bassetti, University of Wisconsin, Madison

Publications

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