Neoadjuvant Gemcitabine, Docetaxel, and Capecitabine in Combination With Stereotactic Radiosurgery

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborator: Sanofi
• 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 the patient's tumor followed by more chemotherapy can increase the chances that the patient's pancreatic tumor can be removed completely.

Condition or disease	Intervention/treatment	Phase
Pancreatic Neoplasms	Drug: GTX (gemcitabine, docetaxel and capecitabine); Radiation: stereotactic body radiation therapy	Phase 2

Detailed Description:

• Cycle 1 and 2:

  • Days 4, 11 and 25, 32 ....gemcitabine 750 mg/m^2 intravenous piggy back (IVPB) over 30 min
  • Days 4, 11 and 25, 32 ....docetaxel 30 mg/m^2 IVPB over 1 hour
  • Days 1-14 and 22-35 ....capecitabine 750 mg/m^2 oral twice daily
  • Each cycle is 21 days long
• SRS: Day 43 ....25 Gy single fraction to the pancreatic tumor gross target volume

• Cycle 3 and 4:

  • Days 54, 61 and 75, 82 ....gemcitabine 750 mg/m^2 IVPB over 30 min
  • Days 54, 61 and 75, 82 ....docetaxel 30 mg/m^2 IVPB over 1 hour
  • Days 51-64 ....capecitabine 750 mg/m^2 oral twice daily
  • Each cycle is 21 days long
• Surgery: Exploratory laparotomy or laparoscopy followed by pancreaticoduodenectomy or central pancreatectomy with or without vein resection and reconstruction as appropriate.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	2 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 2 Study of GTX-SRS: Neoadjuvant Gemcitabine, Docetaxel, and Capecitabine in Combination With Stereotactic Radiosurgery for Borderline Resectable Pancreatic Cancer
Study Start Date :	March 2009
Actual Primary Completion Date :	March 2010
Actual Study Completion Date :	March 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Chemotherapy followed by Radiation Treatment; GTX-SRS: Gemcitabine, Taxotere, Xeloda (GTX)-Stereotactic Radiosurgery (SRS)	Drug: GTX (gemcitabine, docetaxel and capecitabine); GTX: 21 day cycle x 2 Gemcitabine 750mg/m2 on days 4 and 11 Taxotere® (docetaxel) 30 mg/m2 on days 4 and 11 Xeloda® (capecitabine) 750 mg/m2 on days 1-14; Other Names: Gemcitabine; Taxotere®; docetaxel; Xeloda®; capecitabine; Radiation: stereotactic body radiation therapy; stereotactic body radiation therapy (SBRT) 25; Other Name: SBRT

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Resectability [ Time Frame: 6 months per patient ]
   The intent was to have 33 Evaluable Participants and measure the number of surgical resections with negative margins, ie. R0 resection rate. The new treatment would be of interest if the resectability rate was at least 30%. R0 resections were to be scored as those resections in which the common bile duct margin, pancreatic resection margin, retroperitoneal margin were negative for tumor involvement.

Secondary Outcome Measures :

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs). [ Time Frame: 6 months per patient ]
   Investigators planned to review the occurrences of AEs and SAEs according severity by NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0, Acute GI toxicity by Radiation Therapy Oncology Group (RTOG) Gastrointestinal (GI) toxicity scale.
2. Number of Participants With Objective Response [ Time Frame: 6 months per patient ]
   Investigators planned to prospectively evaluate the ability of serum CA19-9 response and positron-emission tomography (PET) / computed tomography(CT) response to predict pathologic treatment response to GTX-SBRT and to determine the correlation of standardized uptake value (SUV) uptake on PET to fiducial marker placement.
3. Number of Participants With Overall Survival [ Time Frame: 6 months per patient ]
   We intended to track the number of participants with overall survival at the projected end of the study period. The study was terminated prematurely.

Eligibility Criteria

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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 < 180o.
  • circumferential tumor abutment with the superior mesenteric artery (SMA) over < 180o.
  • Short segment encasement (360o) 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 - OR - creatinine clearance >60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • total bilirubin < institutional upper limit of normal (ULN). 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.
• Prior malignancy in the last 3 years, except basal cell carcinoma, squamous cell or in-situ cervical cancer.
• 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 PS 3-4
• Pregnant 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
• creatinine clearance < 30 ml/min (Cockcroft-Gault method).
• Patients must not have any comorbid inflammatory conditions of the bowel such as Crohn's Disease.

Contacts and Locations

Locations

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United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Sanofi

Investigators

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Principal Investigator:	Gregory Springett, M.D., Ph.D.	H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Moffitt Cancer Center Clinical Trials website 

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Responsible Party:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT00833859 History of Changes
Other Study ID Numbers:	MCC-15587; IST 14091 ( Other Identifier: Sanofi-Aventis US Inc. )
First Posted:	February 2, 2009
Results First Posted:	May 26, 2011
Last Update Posted:	October 9, 2017
Last Verified:	December 2013

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

stereotactic radiosurgery; borderline resectable pancreatic cancer; gastrointestinal; pancreas

Additional relevant MeSH terms:

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Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gemcitabine; 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