Clinical trial NCT00425841: Stereotactic Radiation Therapy and Combination Chemotherapy in Treating Patients Undergoing Surgery for Locally Advanced Pancreatic Cancer
Official title: Lokal Fortgeschrittenes Pankreas-Karzinom: Stereotaktische Radiotherapie Gefolfgt Von Gemox-Chemotherapie
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: adenocarcinoma of the pancreas
stage III pancreatic cancer
stage II pancreatic cancer
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
First posted: 2007-01-23
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Stereotactic radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Drugs used in chemotherapy, such as gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving stereotactic radiation therapy together with combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving combination chemotherapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well giving stereotactic radiation therapy together with combination chemotherapy works in treating patients undergoing surgery for locally advanced pancreatic cancer.

Detailed description: OBJECTIVES:

Primary

* Determine the clinical response rate in patients undergoing surgery for locally advanced pancreatic cancer treated with stereotactic radiotherapy, gemcitabine hydrochloride, and oxaliplatin.

Secondary

* Determine the toxicity of this regimen in these patients.
* Determine the time to disease progression in patients treated with this regimen.
* Determine the time to death in patients treated with this regimen.
* Determine perioperative morbidity and mortality in patients treated with this regimen.
* Determine the rate of R0 resections in patients treated with this regimen.
* Determine the histologic response rate in these patients.

OUTLINE:

* Neoadjuvant therapy: Patients undergo hypofractionated, stereotactic radiotherapy on days 1-5. Patients also receive gemcitabine hydrochloride IV over 100 minutes on day 1 and oxaliplatin IV over 120 minutes on day 2. Treatment with gemcitabine hydrocloride and oxaliplatin repeats every 2 weeks for 3 courses.
* Surgery: Patients with resectable disease undergo tumor resection. Patients with unresectable disease undergo a second course of neoadjuvant chemoradiotherapy followed by resection.
* Adjuvant therapy: Beginning 3-4 weeks after surgery, patients receive 3 more courses of chemotherapy as in neoadjuvant therapy.

After completion of study treatment, patients are followed every 3 months for up to 2 years.

PROJECTED ACCRUAL: A total of 29 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed adenocarcinoma of the pancreas or intrapancreatic bile duct carcinoma

  * Overall view of image morphology and CA19-9 (\< 500 U/L) demonstrating pancreatic cancer allowed if histologic/cytologic confirmation is unavailable
* Locally advanced disease, meeting 1 of the following criteria:

  * Uncertain R0 resectability dependant on relation to portal vein, sinus confluens, superior mesenteric artery, and superior mesenteric vein (e.g., contact with portal vein, superior mesenteric vein, or arterial vessels, but \< 180° encasement)
  * Unresectable pancreatic cancer (e.g., contact with portal vein, superior mesenteric artery or arterial vessels, \> 180° encasement)
* Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 1 cm by spiral CT scan or MRI

  * Patients with no measurable disease may be assessed for feasibility only
* No distant metastases

PATIENT CHARACTERISTICS:

* ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
* WBC ≥ 3,000/mm³
* Granulocyte count ≥ 2,000/mm³
* Platelet count ≥ 100,000/mm³
* Creatinine clearance \> 30 mL/min
* Bilirubin ≤ 3.0 times upper limit of normal
* AST and ALT ≤ 2.5 times normal
* Alkaline phosphatase ≤ 2.5 times normal
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No secondary malignancy within the past 5 years that was not curatively treated
* No known intolerance to any of the study drugs
* No preexisting polyneuropathy \> grade 1
* No active uncontrolled infection
* No cardiac insufficiency despite optimal medication
* No New York Heart Association class III or IV congestive heart failure
* LVEF ≥ 50% OR shortening fraction ≥ 25%
* No angina pectoris (at rest or under stress) unexplained by interventional cardiology within the past 6 months
* No myocardial infarction within the past 6 months
* No uncontrolled diabetes mellitus
* No other existing serious medical impairments that would preclude study compliance

PRIOR CONCURRENT THERAPY:

* No prior chemotherapy
* No prior radiotherapy to the abdomen

Primary outcomes:
measure: Clinical response rate as assessed by RECIST criteria
Secondary outcomes:
measure: Toxicity as assessed by NCI-CTC criteria
measure: Time to progression
measure: Time to death
measure: Perioperative morbidity and mortality
measure: Rate of R0 resections
measure: Histologic response rate
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Study officials:
affiliation: Technical University of Munich
name: Florian Lordick, MD
role: STUDY_CHAIR
References: