Clinical trial NCT00266097: Oxaliplatin, Gemcitabine, Erlotinib, and Radiation Therapy in Treating Patients With Unresectable and/or Metastatic Pancreatic Cancer or Biliary Tract Cancer
Official title: A Two-Part Phase I Study of the Addition of Oxaliplatin to Gemcitabine, and Then Erlotinib Plus Oxaliplatin to Gemcitabine as Radiosensitizers for Pancreatic and Biliary Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Pancreatic Cancer
Keywords: stage III pancreatic cancer
stage IV pancreatic cancer
unresectable extrahepatic bile duct cancer
unresectable gallbladder cancer
adenocarcinoma of the extrahepatic bile duct
adenocarcinoma of the gallbladder
adenocarcinoma of the pancreas
recurrent pancreatic cancer
recurrent extrahepatic bile duct cancer
recurrent gallbladder cancer
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-12-15
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving oxaliplatin together with gemcitabine, erlotinib, and radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of oxaliplatin, gemcitabine, and erlotinib when given together with radiation therapy in treating patients with unresectable and/or metastatic pancreatic cancer or biliary tract cancer.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose (MTD) of oxaliplatin and gemcitabine hydrochloride when combined with radiotherapy in patients with unresectable and/or metastatic pancreatic or biliary tract adenocarcinoma. (Part 1)
* Determine the MTD of erlotinib hydrochloride and gemcitabine hydrochloride when combined with oxaliplatin at the MTD and radiotherapy in these patients. (Part 2)

OUTLINE: This is a multicenter, nonrandomized, parallel group, uncontrolled, open-label, dose-escalation study of gemcitabine hydrochloride, oxaliplatin, and erlotinib hydrochloride.

* Part 1: Patients receive gemcitabine hydrochloride IV over 30-60 minutes and oxaliplatin IV on day 1. Patients also undergo external beam radiotherapy (EBRT) once daily on days 1-5. Treatment repeats every 7 days for up to 6 courses.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT). Up to 10 patients are treated at the MTD.

* Part 2: Patients receive gemcitabine hydrochloride, oxaliplatin\*, and EBRT as in part 1. Patients also receive oral erlotinib hydrochloride once daily on days 1-5. Treatment repeats every 7 days for up to 6 courses.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and erlotinib hydrochloride until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience DLT. Up to 10 patients are treated at the MTD.

NOTE: \*Patients receive oxaliplatin at the MTD determined in part 1.

After completion of study treatment, patients are followed every 3 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Biopsy confirmed diagnosis of any of the following:

  * Pancreatic carcinoma
  * Ampullary carcinoma
  * Biliary tract (gallbladder or bile duct) carcinoma
* Unresectable and/or biopsy-proven metastatic disease
* Suitable for bimodality therapy, as determined by a medical oncologist and radiation oncologist

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy \> 2 months
* ANC \> 1,500/mm³
* Platelet count \> 100,000/mm³
* Creatinine \< 1.5 mg/dL
* Total bilirubin \< 2 times upper limit of normal (ULN)
* AST \< 3 times ULN (\< 5 times ULN if liver metastases are present)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No known hypersensitivity to platinum agent or gemcitabine hydrochloride
* No serious medical or psychiatric illnesses that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

* No prior radiotherapy to the upper abdomen
* More than 3 weeks since prior chemotherapy
* No prior erlotinib hydrochloride
* At least 5 days since prior and no concurrent CYP3A4 inducer/inhibitor

Primary outcomes:
measure: Maximum tolerated dose (MTD) of oxaliplatin and gemcitabine hydrochloride (Part 1)
timeFrame: 6 weeks
measure: Maximum Tolerated Dose (MTD) of erlotinib hydrochloride and gemcitabine hydrochloride (Part 2)
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Bert H. O'Neil, MD
role: PRINCIPAL_INVESTIGATOR
References: