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

A Phase 2 Study of GTX-SRS: Neoadjuvant Gemcitabine, Docetaxel, and Capecitabine in Combination With Stereotactic Radiosurgery for Borderline Resectable Pancreatic Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Neoplasms
• Intervention / Treatment: Drug: GTX (gemcitabine, docetaxel and capecitabine); Radiation: stereotactic body radiation therapy

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 Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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®; capecitabine; docetaxel; Xeloda®; Radiation: stereotactic body radiation therapy; stereotactic body radiation therapy (SBRT) 25; Other Names: SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Resectability	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.	6 months per patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs).	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.	6 months per patient
Number of Participants With Objective Response	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.	6 months per patient
Number of Participants With Overall Survival	We intended to track the number of participants with overall survival at the projected end of the study period. The study was terminated prematurely.	6 months per patient

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Sanofi

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: January 30, 2009
• First Submitted That Met QC Criteria: January 30, 2009
• First Posted (Estimate): February 2, 2009

Study Record Updates

• Last Update Posted (Actual): October 9, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: pancreas; stereotactic radiosurgery; gastrointestinal; borderline resectable pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gemcitabine; Docetaxel; Capecitabine
• Other Study ID Numbers: MCC-15587; IST 14091 (Other Identifier: Sanofi-Aventis US Inc.)