Stereotactic Body Radiation Therapy and Capecitabine Before Surgery in Treating Patients With Pancreatic Cancer That Can be Removed by Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by University of Wisconsin, Madison
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01918644
First received: August 5, 2013
Last updated: October 11, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
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
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    The number and percent of patients reporting adverse events (all, severe or worse, serious and related) will be quantified for each dose level.


Secondary Outcome Measures:
  • Incidence of 30-day post-operative complications [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Will be expressed as a percentage.

  • Radiological response per Response Evaluation Criteria in Solid Tumors (RECIST) and volumetric measurements [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will be expressed as a percentage.

  • Pathological response, graded based on the College of American Pathologists (CAP) and Ishikawa, Evans, and Chun grading systems [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will be expressed as a percentage.

  • Incidence of margin-negative resection, defined as the absence of viable tumor cells at the inked surgical margin [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will be expressed as a percentage.

  • Loco-regional recurrence free survival, defined with follow-up radiological assessment [ Time Frame: From the point of start of SBRT to the point of recurrence or death, assessed up to 3 years ] [ Designated as safety issue: No ]
    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.

  • OS [ 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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 36
Study Start Date: August 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Names:
  • SBRT
  • stereotactic radiation therapy
  • stereotactic radiotherapy
Drug: capecitabine
Given PO
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Procedure: therapeutic conventional surgery
Undergo definitive surgery
Procedure: magnetic resonance imaging
Optional correlative studies
Other Names:
  • MRI
  • NMR imaging
  • NMRI
  • nuclear magnetic resonance imaging
Other: laboratory biomarker analysis
Optional correlative studies

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.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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 and diagnostic laparoscopy (including cytology)
  • 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 =< 2.5 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) peptic ulcer disease or inflammatory/ irritable bowel disease/ Crohn's disease/ ulcerative colitis/ scleroderma/ rheumatoid arthritis
  • 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, radiation therapy or chemotherapy in the last 5 years, 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 post appropriate therapy at least 2 years ago with controlled prostate-specific antigen (PSA) levels, treated nonmelanoma skin cancer, appropriately treated low grade ductal carcinoma in situ of breast and appropriately treated in-situ cervical cancer)
  • Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, ongoing anti-coagulant therapy or psychiatric illness/social situations that would limit compliance with study requirements
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01918644

Locations
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Mark A. Ritter, MD    608-263-8500    ritter@humonc.wisc.edu   
Contact: Pranshu Mohindra, MD       pmohindra@uwhealth.org   
Principal Investigator: Mark A. Ritter         
Sponsors and Collaborators
University of Wisconsin, Madison
Investigators
Principal Investigator: Mark Ritter University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT01918644     History of Changes
Other Study ID Numbers: RO-12210, NCI-2013-01347, 2013-0645, RO12210, P30CA014520
Study First Received: August 5, 2013
Last Updated: October 11, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Capecitabine
Fluorouracil
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 19, 2014