Oxaliplatin, Gemcitabine, Erlotinib, and Radiation Therapy in Treating Patients With Unresectable and/or Metastatic Pancreatic Cancer or Biliary Tract Cancer

UNC Lineberger Comprehensive Cancer Center

Status and phase: Completed; Phase 1

Conditions: Gallbladder Cancer; Extrahepatic Bile Duct Cancer; Pancreatic Cancer

Treatments: Drug: gemcitabine hydrochloride; Radiation: radiation therapy; Drug: Oxaliplatin; Drug: erlotinib hydrochloride; Drug: oxaliplatin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00266097

CDR0000550061 (Other Identifier)

LCCC 0405

P30CA016086 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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23 participants in 2 patient groups

Part I

Experimental group

Description:

Oxaliplatin + Gemcitabine + Radiation

Treatment:

Drug: oxaliplatin

Radiation: radiation therapy

Drug: gemcitabine hydrochloride

Drug: gemcitabine hydrochloride

Part II

Experimental group

Description:

Erlotinib + Oxaliplatin + Gemcitabine + Radiation

Treatment:

Radiation: radiation therapy

Drug: gemcitabine hydrochloride

Drug: Oxaliplatin

Drug: erlotinib hydrochloride

Drug: gemcitabine hydrochloride