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

Sponsor

UNC Lineberger Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00266097

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Extrahepatic Bile Duct Cancer Gallbladder Cancer Pancreatic Cancer	Drug: erlotinib hydrochloride Drug: gemcitabine hydrochloride Drug: oxaliplatin Radiation: radiation therapy Drug: gemcitabine hydrochloride Drug: Oxaliplatin	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

23 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Aug 1, 2004

Actual Primary Completion Date :

Mar 1, 2009

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part I Oxaliplatin + Gemcitabine + Radiation	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
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.

Arm

Intervention/Treatment

Experimental: Part I

Oxaliplatin + Gemcitabine + Radiation

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

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.

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) of oxaliplatin and gemcitabine hydrochloride (Part 1) [6 weeks]
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
Maximum Tolerated Dose (MTD) of erlotinib hydrochloride and gemcitabine hydrochloride (Part 2) [6 weeks]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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