GTX-RT in Borderline Resectable Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT01754623
• Recruitment Status: Terminated
• First Posted: December 21, 2012
• Results First Posted: August 13, 2015
• Last Update Posted: August 13, 2015
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Study Description

Brief Summary:

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 or disease	Intervention/treatment	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

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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)
• Study Start Date: February 2013
• Actual Primary Completion Date: September 2014
• Actual Study Completion Date: October 2014

Arms and Interventions

Arm

Intervention/treatment

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).

Outcome Measures

Primary Outcome Measures :

1. Margin-negative (R0) Resection Rate [ Time Frame: Up to 3 years ]
   R0 rate for all participants with resection. Margin negative surgery (R0 resection) is an absolute part of the curative treatment of pancreatic cancer.The primary endpoint is correlation of a radio sensitivity index score derived from the microarray analysis and pathologic response on surgical specimens. Tumor regression Rating: R0 (Complete Response). R0 resections are scored as those resections in which the common bile duct margin, pancreatic resection margin, retroperitoneal margin are negative for tumor involvement.

Secondary Outcome Measures :

1. Progression-Free Survival (PFS) at Three Years [ Time Frame: 3 years ]
   PFS is defined as the duration of time from enrollment to time of death or progression of disease, whichever occurs first. Progressive Disease (PD): At least a 20% increase in the longest diameter (LD) of the target lesion or appearance of new lesions at metastatic sites.
2. Overall Survival (OS) Rate [ Time Frame: 12 months ]
   OS at time of analysis, calculated from date of enrollment to date of death from any cause.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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:

Moffitt Cancer Center Clinical Trials website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Strom T, Hoffe SE, Fulp W, Frakes J, Coppola D, Springett GM, Malafa MP, Harris CL, Eschrich SA, Torres-Roca JF, Shridhar R. Radiosensitivity index predicts for survival with adjuvant radiation in resectable pancreatic cancer. Radiother Oncol. 2015 Oct;117(1):159-64. doi: 10.1016/j.radonc.2015.07.018. Epub 2015 Jul 30.

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT01754623
• Other Study ID Numbers: MCC-16932
• First Posted: December 21, 2012
• Results First Posted: August 13, 2015
• Last Update Posted: August 13, 2015
• Last Verified: June 2015

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; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators