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

NCT ID: NCT00266097

Last Updated: 2012-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-08-31
• Study Completion Date: 2011-09-30

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.

Conditions

Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Pancreatic Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part I

Oxaliplatin + Gemcitabine + Radiation

Group Type: EXPERIMENTAL

gemcitabine hydrochloride

Intervention Type: DRUG

Gemcitabine will be given at a dose of 100 mg/m2 for the first cohort and escalated to a fixed dose of 200 mg/m2 for the remaining 3 cohorts

oxaliplatin

Intervention Type: DRUG

Oxaliplatin will be given at 30 mg/m2 weekly for the first two cohorts and then will be dose-escalated to 45 mg/m2 and 60 mg/m2 for the next 2 in cohorts

radiation therapy

Intervention Type: RADIATION

5040 cGy, every week, up to 6 weeks

Part II

Erlotinib + Oxaliplatin + Gemcitabine + Radiation

Group Type: EXPERIMENTAL

erlotinib hydrochloride

Intervention Type: DRUG

Cohort (-1) = 50 mg daily Cohort 1 = 50mg daily Cohort 2= 75 mg daily Cohort 3 = 100mg daily Cohort 4 = 100mg daily Cohort 5 = 150mg daily

radiation therapy

Intervention Type: RADIATION

5040 cGy, every week, up to 6 weeks

gemcitabine hydrochloride

Intervention Type: DRUG

Given weekly at a starting dose of 100mg/m2 in the first 3 cohorts and dose escalated to 200 mg/m2 for the remaining 2 cohorts

Oxaliplatin

Intervention Type: DRUG

The Part II dose of oxaliplatin will be determined by Part I of the study. The dose for Part II will be one dose level increase from the MTD determined in Part I.

Interventions

erlotinib hydrochloride

Cohort (-1) = 50 mg daily Cohort 1 = 50mg daily Cohort 2= 75 mg daily Cohort 3 = 100mg daily Cohort 4 = 100mg daily Cohort 5 = 150mg daily

Intervention Type: DRUG

gemcitabine hydrochloride

Gemcitabine will be given at a dose of 100 mg/m2 for the first cohort and escalated to a fixed dose of 200 mg/m2 for the remaining 3 cohorts

Intervention Type: DRUG

oxaliplatin

Oxaliplatin will be given at 30 mg/m2 weekly for the first two cohorts and then will be dose-escalated to 45 mg/m2 and 60 mg/m2 for the next 2 in cohorts

Intervention Type: DRUG

radiation therapy

5040 cGy, every week, up to 6 weeks

Intervention Type: RADIATION

gemcitabine hydrochloride

Given weekly at a starting dose of 100mg/m2 in the first 3 cohorts and dose escalated to 200 mg/m2 for the remaining 2 cohorts

Intervention Type: DRUG

Oxaliplatin

The Part II dose of oxaliplatin will be determined by Part I of the study. The dose for Part II will be one dose level increase from the MTD determined in Part I.

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bert H. O'Neil, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

Other Identifiers

P30CA016086

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000550061

Identifier Type: OTHER

Identifier Source: secondary_id

LCCC 0405

Identifier Type: -

Identifier Source: org_study_id