PhI Study Of Erbitux & Gemcitabine W/Radiation Therapy For Locally Adv. Pancreas Ca

Study Overview

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

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.

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.

Pancreatic Cancer

BIOLOGICAL: cetuximab
DRUG: gemcitabine hydrochloride
RADIATION: radiation therapy

VICC GI 0466
VU-VICC-GI-0466

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 2007-04-25	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2012-05-16
First Submitted that Met QC Criteria 2007-04-25	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2012-05-18
First Posted (ESTIMATED) 2007-04-27	Results First Posted N/A	Last Verified 2012-05

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:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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. 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 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 inte

Participant Group/Arm

Intervention/Treatment

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.

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

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 inte

Primary Outcome Measures	Measure Description	Time Frame
Maximum Tolerated Dose		Weekly and 4 weeks after last dose of radiation

Secondary Outcome Measures	Measure Description	Time Frame
Dose-limiting toxicity		Weekly and 4 weeks after last dose of radiation
Toxicity		Weekly and 4 weeks after last dose of radiation
Tumor response rate		4 weeks after last dose of radiation and every 3 months

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:

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

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

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

Collaborators and Investigators

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

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Nipun B. Merchant, Vanderbilt-Ingram 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

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Resources

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Clinical Trial Record