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

Vanderbilt University Medical Center

Status and phase

Completed

Phase 1

Conditions

Pancreatic Cancer

Treatments

Radiation: radiation therapy

Drug: gemcitabine hydrochloride

Biological: cetuximab

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00467116

VU-VICC-GI-0466

VICC GI 0466

Details and patient eligibility

About

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.

Full 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.

Enrollment

9 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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