Gemcitabine With Or Without WX-671 In Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed By Surgery

Study Overview

Gemcitabine With or Without WX-671 in Treating Patients With Locally Advanced Pancreatic Cancer That Cannot Be Removed By Surgery

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.

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.

Pancreatic Cancer

DRUG: gemcitabine hydrochloride
DRUG: Serine Proteinase Inhibitor WX-671
DRUG: Serine Proteinase Inhibitor WX-671

CDR0000553460
WILEX-WX-60-004

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2007-07-10	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2012-03-28
First Submitted that Met QC Criteria 2007-07-10	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2012-03-29
First Posted (ESTIMATED) 2007-07-11	Results First Posted N/A	Last Verified 2012-03

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
ACTIVE_COMPARATOR: Gemcitabine	DRUG: gemcitabine hydrochloride 1000 mg/m2 as 30 min i.v. infusion once weekly for 7/8 weeks and then every 3/4 weeks DRUG: Serine Proteinase Inhibitor WX-671 oral, daily DRUG: Serine Proteinase Inhibitor WX-671 oral, daily
EXPERIMENTAL: Gemcitabine plus 200 mg WX-671	DRUG: Serine Proteinase Inhibitor WX-671 oral, daily
EXPERIMENTAL: Gemcitabine plus 400 mg WX-671	DRUG: Serine Proteinase Inhibitor WX-671 oral, daily

Participant Group/Arm

Intervention/Treatment

ACTIVE_COMPARATOR: Gemcitabine

DRUG: gemcitabine hydrochloride

1000 mg/m2 as 30 min i.v. infusion once weekly for 7/8 weeks and then every 3/4 weeks

DRUG: Serine Proteinase Inhibitor WX-671

oral, daily

DRUG: Serine Proteinase Inhibitor WX-671

oral, daily

EXPERIMENTAL: Gemcitabine plus 200 mg WX-671

DRUG: Serine Proteinase Inhibitor WX-671

oral, daily

EXPERIMENTAL: Gemcitabine plus 400 mg WX-671

DRUG: Serine Proteinase Inhibitor WX-671

oral, daily

Primary Outcome Measures	Measure Description	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

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Inclusion criteria:

Locally advanced, unresectable, non-metastatic, histologically proven pancreatic adenocarcinoma (lymph nodes will not be considered metastases)
Exclusion criteria:

Any distant metastases

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
Exclusion criteria:

History of or current primary blood coagulation or bleeding disorders such as hemophilia
Any unrelated illness, e.g., active infection, inflammation, medical condition or laboratory abnormalities, which in the judgment of the investigator might significantly affect the patient's study participation
Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of any drug
Significant cardiac insufficiency (NYHA classification III or IV), presence of unstable angina or myocardial infarction within the previous 6 months, use of ongoing maintenance therapy for life threatening arrhythmia or known pulmonary hypertension
Any secondary malignancies within the last 5 years except for surgically cured non-melanoma skin cancer or cervical carcinoma in situ
Pregnancy (positive serum pregnancy test) or lactation
Known hepatitis B/C or HIV infection
Known hypersensitivity to any of the components in the anti-uPA serine protease inhibitor WX-671 capsules or gemcitabine hydrochloride infusion or other medical reasons for not being able to receive adequate pre-medication (for example, antihistamine or anti-inflammatory agents)

Permitted:

Growth factors for treatment (not prophylaxis, i.e., epoetin alfa), analgesics, blood transfusions, antibiotics, bisphosphonates, other hormonal therapy for contraceptive practice, replacement therapy such as thyroid replacement or adrenal insufficiency as appropriate and medications for acute or chronic conditions not listed under the exclusion criteria
Embolization (i.e. for hematuria)
Subjects can receive blood transfusions as medically appropriate during the study

Subjects who require a blood transfusion during screening must have stable hemoglobin (≥9.0 g/dL [5.6 mmol/L]) without the need for further transfusions within 2 weeks before the first dose of anti-uPA serine protease inhibitor WX-671 to remain eligible
Prophylactic use of growth factors to support neutrophils
Prohibited:

Anticoagulant or thrombolytic therapy within four weeks prior to start of treatment (except low dose anticoagulant therapy with unfractionated heparin ≤ 15000 IU/d, low molecular weight heparin ≤ 5000 IE anti-Xa activity or acetyl salicylic acid ≤ 100 mg/d at the discretion of the investigator)
Anticancer therapies such as biologic therapy and chemotherapy (other than study drugs)
Radiation therapy (during the treatment phase of the protocol; increased bone pain not controlled by medication and requiring palliative therapy will be considered disease progression)
Laser treatment
Any other investigational agent
Thalidomide
Immunosuppressive therapies (inhaled or replacement dose corticosteroids are permitted).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_CHAIR: Carola Mala, PhD, Heidelberg Pharma AG

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

Learn

Resources

PatientS

Caregivers

Clinical Trial Record