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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00266097
First received: December 13, 2005
Last updated: March 5, 2012
Last verified: March 2012

December 13, 2005
March 5, 2012
August 2004
March 2009   (final data collection date for primary outcome measure)
  • Maximum tolerated dose (MTD) of oxaliplatin and gemcitabine hydrochloride (Part 1) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    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
  • - To determine the maximum tolerated combination (MTC) of Oxaliplatin and gemcitabine when used with radiation therapy.
  • Phase I
  • Phase II
  • - To determine the median overall survival for patients with locally advanced, unresectable pancreatic cancer treated at the doses determined in the phase I cohort.
Complete list of historical versions of study NCT00266097 on ClinicalTrials.gov Archive Site
Not Provided
  • - Progression free survival at 6 and 12 months
  • - Rate of CA 19-9 response
Not Provided
Not Provided
 
Oxaliplatin, Gemcitabine, Erlotinib, and Radiation Therapy in Treating Patients With Unresectable and/or Metastatic Pancreatic Cancer or Biliary Tract Cancer
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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Extrahepatic Bile Duct Cancer
  • Gallbladder Cancer
  • Pancreatic Cancer
  • 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 I
    Oxaliplatin + Gemcitabine + Radiation
    Interventions:
    • Drug: gemcitabine hydrochloride
    • Drug: oxaliplatin
    • Radiation: radiation therapy
  • Experimental: Part II
    Erlotinib + Oxaliplatin + Gemcitabine + Radiation
    Interventions:
    • Drug: erlotinib hydrochloride
    • Radiation: radiation therapy
    • Drug: gemcitabine hydrochloride
    • Drug: Oxaliplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
23
September 2011
March 2009   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00266097
LCCC 0405, P30CA016086, CDR0000550061
Yes
UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
National Cancer Institute (NCI)
Principal Investigator: Bert H. O'Neil, MD UNC Lineberger Comprehensive Cancer Center
UNC Lineberger Comprehensive Cancer Center
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP