PhI Study of Erbitux & Gemcitabine w/Radiation Therapy for Locally Adv. Pancreas Ca

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Nipun Merchant, MD, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier:
NCT00467116
First received: April 25, 2007
Last updated: May 16, 2012
Last verified: May 2012
  Purpose

RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and help kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Cetuximab may also stop the growth of tumor cells by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Gemcitabine and cetuximab may make tumor cells more sensitive to radiation therapy. Giving gemcitabine together with cetuximab and radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of gemcitabine when given together with cetuximab and radiation therapy in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.


Condition Intervention Phase
Pancreatic Cancer
Biological: cetuximab
Drug: gemcitabine hydrochloride
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Erbitux and Gemcitabine With Radiation Therapy for Locally Advanced Pancreas Cancer

Resource links provided by NLM:


Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose [ Time Frame: Weekly and 4 weeks after last dose of radiation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Dose-limiting toxicity [ Time Frame: Weekly and 4 weeks after last dose of radiation ] [ Designated as safety issue: Yes ]
  • Toxicity [ Time Frame: Weekly and 4 weeks after last dose of radiation ] [ Designated as safety issue: Yes ]
  • Tumor response rate [ Time Frame: 4 weeks after last dose of radiation and every 3 months ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: October 2005
Study Completion Date: October 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Therapeutic Intervention Biological: cetuximab
400mg/m2 initial dose week 1; followed by 250mg/m2/weekly starting week 2 with gemcitabine at fixed dose rate (10 mg/m2/min) + XRT. Cetuximab will start 1 week prior to all other treatment.
Other Name: Erbitux
Drug: gemcitabine hydrochloride

Dose Level Gemcitabine dose Gemcitabine infusion

-1 150mg/m2 15 Minutes 0 200mg/m2 20 minutes

  1. 300mg/m2 30 minutes
  2. 400mg/m2 40 minutes
Other Name: Gemzar
Radiation: radiation therapy

50.4 Gy, 28 fractions, 5.5 weeks (1.8 Gy/day). A cone down after 45 Gy will be performed to encompass gross disease with a margin of 1-1.5 cm.

The prescription point will be designated at the intersection of the multiple beams.

There are no planned interruptions > 3 days.

Other Name: Radiation Therapy

Detailed Description:

OBJECTIVES:

  • Determine the maximum tolerated dose of gemcitabine hydrochloride when administered with cetuximab and radiotherapy in patients with unresectable locally advanced pancreatic or periampullary region cancer.
  • Determine the toxicity of this regimen in these patients.

OUTLINE: This is a dose-escalation study of gemcitabine hydrochloride.

Patients receive cetuximab IV over 1-2 hours once weekly in weeks 1-7 and gemcitabine hydrochloride IV over 15-40 minutes once weekly in weeks 2-7. Patients also undergo radiotherapy 5 days a week in weeks 2-7. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride 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.

After completion of study treatment, patients are followed for 30 days and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 12-30 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the pancreas (head, body, or tail) or periampullary region, meeting both of the following criteria:

    • Unresectable disease
    • Locally advanced disease
  • Measurable or evaluable disease by CT scan or MRI
  • No evidence of metastatic disease outside of the planned irradiation field
  • ECOG performance status 0-2
  • WBC ≥ 3,000/mm³
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin ≥ 8.5 g/dL
  • AST and ALT ≤ 5 times upper limit of normal
  • Bilirubin ≤ 2.0 mg/dL
  • Creatinine ≤ 2.0 mg/dL
  • No clinical indication of compromised function of nonirradiated kidney
  • No secondary malignancies within the past 5 years except for resected nonmelanoma skin cancer or carcinoma in situ of the cervix
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

Exclusion Criteria:

  • No acute hepatitis
  • No known HIV infection
  • No other active or uncontrolled infection
  • No significant history of uncontrolled cardiac disease, including any of the following:

    • Hypertension
    • Unstable angina
    • Myocardial infarction within the past 6 months
    • Congestive heart failure
    • Cardiomyopathy with decreased ejection fraction
  • No prior severe infusion reaction to a monoclonal antibody

PRIOR CONCURRENT THERAPY:

  • No prior radiotherapy to planned field of treatment
  • No prior therapy that specifically and directly targets EGFR pathway
  • At least 14 days since prior surgery or biopsy
  • At least 28 days since prior bypass procedures
  • More than 5 years since prior and no other concurrent chemotherapy
  • No other concurrent investigational agent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00467116

Locations
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Investigators
Principal Investigator: Nipun B. Merchant Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: Nipun Merchant, MD, Professor of Surgery and Cancer Biology; Gastrointestinal Surgical Oncologist, Vanderbilt-Ingram Cancer Center
ClinicalTrials.gov Identifier: NCT00467116     History of Changes
Other Study ID Numbers: VICC GI 0466, VU-VICC-GI-0466
Study First Received: April 25, 2007
Last Updated: May 16, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
stage III pancreatic cancer
adenocarcinoma of the pancreas
stage II pancreatic cancer
recurrent pancreatic cancer

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Cetuximab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 22, 2014