Clinical trial NCT00833859: Neoadjuvant Gemcitabine, Docetaxel, and Capecitabine in Combination With Stereotactic Radiosurgery
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Neoplasms
Keywords: stereotactic radiosurgery
borderline resectable pancreatic cancer
gastrointestinal
pancreas
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2009-02-02
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Resectability
timeFrame: 6 months per patient
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs).
timeFrame: 6 months per patient
measure: Number of Participants With Objective Response
timeFrame: 6 months per patient
measure: Number of Participants With Overall Survival
timeFrame: 6 months per patient
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Gregory Springett, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: