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

NCT ID: NCT00467116

Last Updated: 2012-05-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2007-10-31

Brief Summary

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.

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Therapeutic Intervention

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

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.

gemcitabine hydrochloride

Intervention Type: DRUG

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 therapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: BIOLOGICAL

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

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Other Intervention Names

Erbitux; Gemzar

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Vanderbilt-Ingram Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Nipun Merchant, MD

Professor of Surgery and Cancer Biology; Gastrointestinal Surgical Oncologist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nipun B. Merchant

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt-Ingram Cancer Center

Locations

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

VU-VICC-GI-0466

Identifier Type: -

Identifier Source: secondary_id

VICC GI 0466

Identifier Type: -

Identifier Source: org_study_id