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

A Phase I Study of Erbitux and Gemcitabine With Radiation Therapy for Locally Advanced Pancreas Cancer

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Biological: cetuximab; Drug: gemcitabine hydrochloride; Radiation: 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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

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.; Other Names: Erbitux; Drug: gemcitabine hydrochloride; Dose Level Gemcitabine dose Gemcitabine infusion -1 150mg/m2 15 Minutes 0 200mg/m2 20 minutes; 300mg/m2 30 minutes; 400mg/m2 40 minutes; Other Names: 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Nipun B. Merchant, Vanderbilt-Ingram Cancer Center

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: April 25, 2007
• First Submitted That Met QC Criteria: April 25, 2007
• First Posted (Estimate): April 27, 2007

Study Record Updates

• Last Update Posted (Estimate): May 18, 2012
• Last Update Submitted That Met QC Criteria: May 16, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: recurrent pancreatic cancer; adenocarcinoma of the pancreas; stage III pancreatic cancer; stage II pancreatic cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Gemcitabine; Cetuximab
• Other Study ID Numbers: VICC GI 0466; VU-VICC-GI-0466