Clinical trial NCT00467116: PhI Study of Erbitux & Gemcitabine w/Radiation Therapy for Locally Adv. Pancreas Ca
Official title: A Phase I Study of Erbitux and Gemcitabine With Radiation Therapy for Locally Advanced Pancreas Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: stage III pancreatic cancer
adenocarcinoma of the pancreas
stage II pancreatic cancer
recurrent pancreatic cancer
Lead sponsor: Vanderbilt-Ingram Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-04-27
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum Tolerated Dose
timeFrame: Weekly and 4 weeks after last dose of radiation
Secondary outcomes:
measure: Dose-limiting toxicity
timeFrame: Weekly and 4 weeks after last dose of radiation
measure: Toxicity
timeFrame: Weekly and 4 weeks after last dose of radiation
measure: Tumor response rate
timeFrame: 4 weeks after last dose of radiation and every 3 months
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: Vanderbilt-Ingram Cancer Center
name: Nipun B. Merchant
role: PRINCIPAL_INVESTIGATOR
References: