Clinical trial NCT00424827: A Trial of Chemo & Radiation Therapy for Pancreatic Cancer
Official title: A Phase II Trial of Cetuximab, Gemcitabine, 5-Fluorouracil and Radiation Therapy in Locally Advanced Non-metastatic Pancreatic Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: pancreatic cancer, gemcitabine, 5-FU, cetuximab, radiation
Lead sponsor: University of Massachusetts, Worcester
Sponsor class: OTHER
First posted: 2007-01-22
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, non-randomized, combination study of cetuximab, gemcitabine, 5-FU, and external beam radiotherapy in patients with locally advanced, non-metastatic pancreatic cancer.

Detailed description: During cycle I (chemoradiation), gemcitabine (200 mg/m2) and cetuximab 400mg/m2 initial dose followed by 250mg/m2 IV weekly will be given with continuous infusion 5-FU (200 mg/m2/day) delivered 5 of every 7 days and concurrent external beam radiation therapy. Cetuximab, gemcitabine and 5-FU will begin on the first week of external beam radiotherapy and will continue throughout the course of external beam radiation therapy, and will be discontinued following the conclusion of external beam radiation therapy. All patients will have a central venous access device placed to facilitate chemotherapy administration.

During cycles 2 through 5 (chemotherapy), gemcitabine will be administered at a dose of 1000 mg/m2 over 30 minutes followed by cetuximab at a dose of 250mg/m2 over 30 minutes weekly for 3 weeks followed by one-week rest for four cycles.

Eligibility criteria: Inclusion Criteria:

* Histological confirmation of pancreatic adenocarcinoma is required.
* Only patients with unresectable, non-metastatic tumors are eligible.
* Documentation of disease extent by endoscopic ultrasound and either laparotomy or laparoscopy must be performed within 42 days of registration.
* All patients will also be assessed by chest x-ray and abdominal-pelvic CT scan.
* Confirmation of palliative surgical bypass at the time of laparotomy or whether a biliary stent was placed will be requested.
* Disease must be locoregional and not amenable to surgery based on one or more of the following criteria:

  * size of pancreatic tumor \> 5 cm.
  * lymph nodes (bulky, \> 2 cm, but within a radiation port)
  * vascular involvement or impingement of major vessels (superior mesenteric artery, superior mesenteric vein, portal vein, hepatic artery).
  * invasion into the adjacent structures.
* Patients with either measurable or evaluable disease are eligible.
* Patients with evidence of peritoneal seeding by malignancy are not eligible for the study.
* Patients with other evidence of metastatic disease are not eligible.
* Patients with concurrent malignancy of any site, except limited basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, are ineligible.
* Patients with any other malignancy within 5 years of study entry, except curatively treated basal cell carcinoma or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, are ineligible.
* Patients may not have had prior therapy for carcinoma of the pancreas, nor prior abdominal radiation therapy.
* Age \> 18 years.
* CTC performance status \< 2.
* No myocardial infarction in the past six months.
* No major surgery in the past two weeks.
* No uncontrolled serious medical or psychiatric illness.
* Required Initial Laboratory Data:

  * Total bilirubin \< 2.0 mg/dl
  * AST \< 3x upper limits of normal.
  * Serum creatinine \< 2.0 mg/dl
  * WBC \> 3,000/mm3 (ANC\>1500/mm3)
  * Platelets \> 100,000 mm3
  * CA 19-9
* Required Diagnostic procedures:

  * Chest X-ray
  * Abdominal pelvic CT scan
  * EUS
  * Staging laparoscopy or staging laparotomy

Exclusion Criteria:

Enrollment in this trial will be limited to patients for whom protocol therapy is safe and appropriate. Physicians should consider the risks and benefits of therapy together with all relevant medical and other considerations in deciding whether this protocol is appropriate for a particular patient. Specific considerations include:

* Psychiatric illness which would prevent the patient from giving informed consent.
* Serious medical illness such as uncontrolled infection, severe cardiovascular disease including recent (\< 6 months) myocardial infarction or uncontrolled congestive heart failure, or other serious illness which would limit anticipated survival to \< 12 weeks.
* Protocol treatment would pose significant risk to an unborn child. Pregnant women should not be enrolled, and women of child-bearing age should be strongly encouraged to practice effective birth control during and for three months after the trial.
* Inability to swallow medication. Patients should have adequate, unassisted oral intake.

Primary outcomes:
measure: Progression-free Survival of Patients With Locally Advanced Pancreatic Cancer Treated With Concurrent Gemcitabine, 5-FU, Cetuximab and External Beam Radiation Therapy.
timeFrame: 1-year
Secondary outcomes:
measure: Biomarker Response to Chemoradiation Therapy
timeFrame: 1-year
measure: Resection Rate
timeFrame: 1-Year
measure: Overall Survival
timeFrame: Up to 2 years
measure: Toxicity Associated With This Regimen.
timeFrame: 1-Year
Other outcomes:
Locations:
Study officials:
affiliation: University of Massachusetts, Worcester
name: Venu Bathini, MD
role: PRINCIPAL_INVESTIGATOR
References: