GTX-RT in Borderline Resectable Pancreatic Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01754623
First received: December 18, 2012
Last updated: September 24, 2014
Last verified: September 2014
  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:


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).

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.
  • 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
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: NCT01754623

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
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:
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: September 24, 2014
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
Gemcitabine
Fluorouracil
Capecitabine
Docetaxel
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on October 19, 2014