Oxaliplatin, Gemcitabine, Erlotinib, And Radiation Therapy In Treating Patients With Unresectable And/or Metastatic Pancreatic Cancer Or Biliary Tract Cancer

Study Overview

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

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.

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.

Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Pancreatic Cancer

DRUG: erlotinib hydrochloride
DRUG: gemcitabine hydrochloride
DRUG: oxaliplatin
RADIATION: radiation therapy
DRUG: gemcitabine hydrochloride
DRUG: Oxaliplatin

LCCC 0405
P30CA016086 (U.S. NIH Grant/Contract)
CDR0000550061 (OTHER Identifier) (OTHER: PDQ number)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2005-12-13	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2012-03-05
First Submitted that Met QC Criteria 2005-12-13	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2012-03-07
First Posted (ESTIMATED) 2005-12-15	Results First Posted N/A	Last Verified 2012-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Crossover

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Part I Oxaliplatin + Gemcitabine + Radiation	DRUG: 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 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 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 RADIATION: radiation therapy 5040 cGy, every week, up to 6 weeks DRUG: 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 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.
EXPERIMENTAL: Part II Erlotinib + Oxaliplatin + Gemcitabine + Radiation	DRUG: 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 RADIATION: radiation therapy 5040 cGy, every week, up to 6 weeks DRUG: 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 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.

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Part I

Oxaliplatin + Gemcitabine + Radiation

DRUG: 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

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

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

RADIATION: radiation therapy

5040 cGy, every week, up to 6 weeks

DRUG: 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

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.

EXPERIMENTAL: Part II

Erlotinib + Oxaliplatin + Gemcitabine + Radiation

DRUG: 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

RADIATION: radiation therapy

5040 cGy, every week, up to 6 weeks

DRUG: 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

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.

Primary Outcome Measures	Measure Description	Time Frame
Maximum tolerated dose (MTD) of oxaliplatin and gemcitabine hydrochloride (Part 1)	The MTC of Oxaliplatin and gemcitabine is defined as the combination for which the rate of toxicities that cause dose reductions plus twice the rate of dsoe limiting toxicity (DLT) is equal to 0.5	6 weeks
Maximum Tolerated Dose (MTD) of erlotinib hydrochloride and gemcitabine hydrochloride (Part 2)	The highest dose for which the observed dose reduction rate plus twice the dose limiting toxicity (DLT) rate does not exceed 0.5 will be declared the MTD	6 weeks

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Bert H. O'Neil, MD, UNC Lineberger Comprehensive Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record