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

March 5, 2012 updated by: UNC Lineberger Comprehensive Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

23

Phase

  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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
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
Experimental: Part II
Erlotinib + 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
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: 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: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose (MTD) of oxaliplatin and gemcitabine hydrochloride (Part 1)
Time Frame: 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
6 weeks
Maximum Tolerated Dose (MTD) of erlotinib hydrochloride and gemcitabine hydrochloride (Part 2)
Time Frame: 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
6 weeks

Collaborators and Investigators

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

Sponsor

UNC Lineberger Comprehensive Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Bert H. O'Neil, MD, UNC Lineberger Comprehensive Cancer Center

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 Major Dates

Study Start

August 1, 2004

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

September 1, 2011

Study Registration Dates

First Submitted

December 13, 2005

First Submitted That Met QC Criteria

December 13, 2005

First Posted (Estimate)

December 15, 2005

Study Record Updates

Last Update Posted (Estimate)

March 7, 2012

Last Update Submitted That Met QC Criteria

March 5, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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