GTX-RT in Borderline Resectable Pancreatic Cancer - Full Text View

Purpose

The purpose of this study is to find out if a program of intensive chemotherapy with gemcitabine, docetaxel and capecitabine followed by an advanced form of focused radiation aimed at participant's tumor followed by more chemotherapy can increase the chances that the participant's pancreatic tumor can be removed completely.

Condition	Intervention	Phase
Pancreatic Cancer	Drug: capecitabine Drug: gemcitabine Drug: docetaxel Radiation: stereotactic body radiation therapy (SBRT) Other: restaging review after radiation Procedure: surgery Drug: 5-Fluorouracil	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Validation of a Radiation Response Signature in Borderline Resectable Pancreatic Cancer Patients Treated With Induction Chemotherapy Followed by Stereotactic Body Radiation Therapy (SBRT)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Fluorouracil Gemcitabine Docetaxel Gemcitabine hydrochloride Capecitabine

U.S. FDA Resources

Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:

Margin-negative (R0) Resection Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The primary endpoint is correlation of a radiosensitivity index score derived from the microarray analysis and pathologic response on surgical specimens. Tumor regression Rating: R0 (Complete Response); R1 (Moderate Response); R2 (Minimal Response); R3 (No Response).
Overall Survival (OS) Rate [ Time Frame: 3 years ] [ Designated as safety issue: No ]
OS will be calculated from date of enrollment to date of death from any cause. Investigators will also compare OS between resected and non-resected patients. Comparative analysis will be performed by Kaplan-Meier analysis and 2-sided log-rank test.

Secondary Outcome Measures:

Progression-Free Survival (PFS) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Progression-Free Survival (PFS) PFS is defined as the duration of time from enrollment to time of death or progression of disease, whichever occurs first. Investigators will also compare PFS between resected and non-resected patients. Comparative analysis will be performed by Kaplan-Meier analysis and 2-sided log-rank test.

Estimated Enrollment:	35
Study Start Date:	February 2013
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Chemotherapy Followed by Radiation Treatment Gemcitabine, Taxotere, Xeloda (GTX): 21 day cycle x 3 Gemcitabine 750mg/m^2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m^2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m^2 on days 1-14 Radiation: stereotactic body radiation therapy stereotactic body radiation therapy (SBRT). After radiation, participants will be re-evaluated for surgery.	Drug: capecitabine Treatment will begin with the first round of chemotherapy. Each round of chemotherapy will take 21 days. Each round or cycle will start with participants taking capecitabine pills. Participants will take tablets of capecitabine (Xeloda®) twice per day for 14 days followed by 7 days without capecitabine. Other Name: Xeloda® Drug: gemcitabine On the fourth day of the cycle, participants will be treated with gemcitabine and docetaxel. First, this will consist of placing gemcitabine (Gemzar®) in a bag of fluid and giving it by vein over 30 minutes. Other Name: Gemzar® Drug: docetaxel On the fourth day of the cycle, participants will be treated with gemcitabine and docetaxel. After the gemcitabine, participants will receive docetaxel (Taxotere®) in a bag of fluid over 1 hour. Other Name: Taxotere® Radiation: stereotactic body radiation therapy (SBRT) 30/40 Gy to pancreatic tumor/area of borderline resectability Other Name: SBRT Other: restaging review after radiation After radiation, participants will be re-evaluated for surgery. Patients who have Complete Response (CR), Partial Response (PR) or stable disease (SD) will proceed with surgical exploration and resection provided they are suitable fit for surgery in the judgment of the surgical oncologist. Patients who have local progression on imaging scan will be offered conventional 5-Fluorouracil based intensity-modulated radiation therapy (IMRT). If no surgery: then chemotherapy. If surgery: chemotherapy will be given based on response. Procedure: surgery Non-metastatic patients who are deemed resectable after neoadjuvant therapy will be taken to surgery. After surgery, chemotherapy will be given based on response. Drug: 5-Fluorouracil Patients who have local progression on imaging scan will be offered conventional 5-Fluorouracil based intensity-modulated radiation therapy (IMRT).

Arms

Assigned Interventions

Experimental: Chemotherapy Followed by Radiation Treatment

Gemcitabine, Taxotere, Xeloda (GTX): 21 day cycle x 3 Gemcitabine 750mg/m^2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m^2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m^2 on days 1-14 Radiation: stereotactic body radiation therapy stereotactic body radiation therapy (SBRT).

After radiation, participants will be re-evaluated for surgery.

Drug: capecitabine

Treatment will begin with the first round of chemotherapy. Each round of chemotherapy will take 21 days. Each round or cycle will start with participants taking capecitabine pills. Participants will take tablets of capecitabine (Xeloda®) twice per day for 14 days followed by 7 days without capecitabine.

Other Name: Xeloda®

Drug: gemcitabine

On the fourth day of the cycle, participants will be treated with gemcitabine and docetaxel. First, this will consist of placing gemcitabine (Gemzar®) in a bag of fluid and giving it by vein over 30 minutes.

Other Name: Gemzar®

Drug: docetaxel

On the fourth day of the cycle, participants will be treated with gemcitabine and docetaxel. After the gemcitabine, participants will receive docetaxel (Taxotere®) in a bag of fluid over 1 hour.

Other Name: Taxotere®

Radiation: stereotactic body radiation therapy (SBRT)

30/40 Gy to pancreatic tumor/area of borderline resectability

Other Name: SBRT

Other: restaging review after radiation

After radiation, participants will be re-evaluated for surgery. Patients who have Complete Response (CR), Partial Response (PR) or stable disease (SD) will proceed with surgical exploration and resection provided they are suitable fit for surgery in the judgment of the surgical oncologist. Patients who have local progression on imaging scan will be offered conventional 5-Fluorouracil based intensity-modulated radiation therapy (IMRT). If no surgery: then chemotherapy. If surgery: chemotherapy will be given based on response.

Procedure: surgery

Non-metastatic patients who are deemed resectable after neoadjuvant therapy will be taken to surgery. After surgery, chemotherapy will be given based on response.

Drug: 5-Fluorouracil

Patients who have local progression on imaging scan will be offered conventional 5-Fluorouracil based intensity-modulated radiation therapy (IMRT).

Detailed Description:

Investigators plan to conduct a prospective pilot phase II trial of GTX-SBRT as neoadjuvant treatment of borderline resectable pancreatic cancer. After informed consent, pretreatment pancreatic tumor tissues will be collected and immediately frozen at the time of staging endoscopic ultrasound (EUS). Ribonucleic acid (RNA) will be extracted from tumor specimens and run on microarray analysis to determine radiosensitivity index score. Borderline resectable (BR) patients will be treated with 3 cycles of GTX chemotherapy followed by SBRT. They will be restaged and evaluated for resectability 3 to 4 weeks later. Non-metastatic patients who are deemed resectable after neoadjuvant therapy will be taken to surgery.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients must have histologically or cytologically confirmed pancreatic adenocarcinoma that is borderline resectable disease. Borderline resectable lesions are defined as:
- circumferential tumor abutment with the superior mesenteric vein (SMV) or portal vein (PV) or SMV/PV confluence over </= 180°
- circumferential tumor abutment with the superior mesenteric artery (SMA) over </= 180°
- Short segment encasement (360°) of the PV or SMV that is amenable to partial vein resection and reconstruction
- encasement of the gastroduodenal artery up to the origin of the hepatic artery
Patients must have measurable disease
No previous chemotherapy or radiation to the pancreas
Eastern Cooperative Oncology Group (ECOG) performance status </= 2 (Karnofsky >/= 60%)
Patients must have normal organ and marrow function as defined below:
- leukocytes >/= 3,000/μL
- absolute neutrophil count >/= 1,000/ μL
- platelets >/= 100,000/ μL
- creatinine within normal institutional limits (ULN)
- total bilirubin will allow for 2x the upper limit of the institution. Patients may have biliary stents or drains to lower total bilirubin to this range.
- aspartate aminotransferase (AST)[serum glutamic oxaloacetic transaminase(SGOT)]/alanine aminotransferase (ALT)[serum glutamic pyruvic transaminase(SGPT)] ;AST and ALT may be up to 2.5 times ULN if alkaline phosphatase < ULN; or alkaline phosphatase may be up to 4 times ULN if AST and ALT are < ULN.
Has a negative serum or urine pregnancy test within 7 days prior to initiation of therapy (female patients of childbearing potential). Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Patients will agree to continue contraception for 30 days from the date of the last study drug administration.
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Patients with metastatic disease are ineligible.
Patients who have had prior chemotherapy for pancreatic adenocarcinoma
Patients who have received prior radiation to an abdominal site are not eligible.
Patients with peripheral neuropathy >/= grade 2
Patients with a history of severe hypersensitivity reaction to Taxotere (docetaxel), other drugs formulated with polysorbate 80, gemcitabine, or capecitabine
Patients may not be receiving any other investigational agents.
ECOG Performance Status 3-4
Pregnant or breast-feeding women are excluded from this study because gemcitabine,capecitabine, and docetaxel are Class D agents with the potential for teratogenic or abortifacient effects.
Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Patients must not have any comorbid inflammatory conditions of the bowel such as Crohn's Disease.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01754623

Locations

United States, Florida
H. Lee Moffitt Cancer Center and Research Institute	Recruiting
Tampa, Florida, United States, 33612
Contact: Michael Rowland 813-745-1157 michael.rowland@moffitt.org
Principal Investigator: Ravi Shridhar, M.D., Ph.D.
Sub-Investigator: Gregory Springett, M.D.
Sub-Investigator: Sarah Hoffe, M.D.
Sub-Investigator: Pamela Hodul, M.D.
Sub-Investigator: Jason Klapman, M.D.
Sub-Investigator: Shivakumar Vignesh, M.D.

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Investigators

Principal Investigator:

Ravi Shridhar, M.D., Ph.D.

H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Moffitt Cancer Center Clinical Trials website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT01754623 History of Changes
Other Study ID Numbers:	MCC-16932
Study First Received:	December 18, 2012
Last Updated:	March 1, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

Pancreas
Pancreatic
Neoplasms
Stereotactic
Radiosurgery
Borderline
Resectable

Gastrointestinal
Gemcitabine
Capecitabine
Fluorouracil
Docetaxel
SBRT
GTX Chemotherapy

Additional relevant MeSH terms:

Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Fluorouracil
Gemcitabine
Capecitabine
Docetaxel
Antimetabolites

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on May 19, 2013