Pancreatic Cancer
Conditions
Keywords
recurrent pancreatic cancer, stage III pancreatic cancer, adenocarcinoma of the pancreas
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. WX-671 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with WX-671 may kill more tumor cells. PURPOSE: This randomized phase II trial is studying how well gemcitabine works when given together with WX-671 or when given alone in treating patients with locally advanced pancreatic cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES: Primary * Assess the antitumor activity of two different doses of anti-uPA serine protease inhibitor WX-671 when given in combination with gemcitabine hydrochloride in patients with locally advanced unresectable pancreatic cancer. * Compare the efficacy, in terms of response rate, progression-free survival, time to first metastasis, overall survival, and tumor and uPA system-related markers, of these regimens in these patients. * Compare the safety, in terms of vital signs, ECG, biochemistry, hematology (including coagulation), and adverse events, of these regimens. OUTLINE: This is an open-label, randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms. * Arm I: Patients receive of oral anti-uPA serine protease inhibitor WX-671 once daily in weeks 1-8 (weeks 1-4 of each subsequent course) and gemcitabine hydrochloride IV over 30 minutes once weekly in weeks 1-7 (weeks 1-3 of each subsequent course) of course 1. All subsequent courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. * Arm II: Patients receive oral anti-uPA serine protease inhibitor WX-671 (at a lower dose than in arm I) once daily in weeks 1-8 (weeks 1-4 of each subsequent course) and gemcitabine hydrochloride IV over 30 minutes once weekly in weeks 1-7 (weeks 1-3 of each subsequent course) of course 1. All subsequent courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. * Arm III: Patients receive gemcitabine hydrochloride IV over 30 minutes once weekly in weeks 1-7 (weeks 1-3 of each subsequent course) of course 1. All subsequent courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Interventions
DRUGgemcitabine hydrochloride
1000 mg/m2 as 30 min i.v. infusion once weekly for 7/8 weeks and then every 3/4 weeks
DRUGSerine Proteinase Inhibitor WX-671
oral, daily
Sponsors
Heidelberg Pharma AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Inclusion criteria: * Locally advanced, unresectable, non-metastatic, histologically proven pancreatic adenocarcinoma (lymph nodes will not be considered metastases) *
Exclusion criteria
* Any distant metastases PATIENT CHARACTERISTICS: * Inclusion criteria: * ECOG performance status ≤ 1 * Life expectancy \> 12 weeks * Normal 12-lead ECG or only clinically insignificant abnormalities in the judgment of the investigator * Female patients of child-bearing potential will be required to use an effective method of birth control for the duration of the study to prevent pregnancy * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 9 g/dL * Total bilirubin ≤ 1.5 times ULN * AST and ALT ≤ 2.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN * Creatinine ≤ 2 times ULN or creatinine clearance \> 45 mL/min *
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy, in terms of response rate, progression-free survival, time to first metastasis, overall survival, and tumor and uPA system-related markers | 3 years |
| Safety, in terms of vital signs, ECG, biochemistry, hematology (including coagulation), and adverse events | 3 years |
Countries
Germany, Hungary, Italy, Russia, Spain, Ukraine
Outcome results
None listed