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

NCT ID: NCT00499265

Last Updated: 2012-03-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2010-05-31

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.

Conditions

Pancreatic Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gemcitabine

Group Type: ACTIVE_COMPARATOR

gemcitabine hydrochloride

Intervention Type: DRUG

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

Gemcitabine plus 200 mg WX-671

Group Type: EXPERIMENTAL

Serine Proteinase Inhibitor WX-671

Intervention Type: DRUG

oral, daily

Gemcitabine plus 400 mg WX-671

Group Type: EXPERIMENTAL

Serine Proteinase Inhibitor WX-671

Intervention Type: DRUG

oral, daily

Interventions

gemcitabine hydrochloride

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

Intervention Type: DRUG

Serine Proteinase Inhibitor WX-671

oral, daily

Intervention Type: DRUG

Serine Proteinase Inhibitor WX-671

oral, daily

Intervention Type: DRUG

Other Intervention Names

GEMZAR; MESUPRON; MESUPRON

Eligibility Criteria

Inclusion Criteria

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

• 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

• Any distant metastases

PATIENT CHARACTERISTICS:

• 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)

PRIOR CONCURRENT THERAPY:

• Permitted:

• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heidelberg Pharma AG

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carola Mala, PhD

Role: STUDY_CHAIR

Heidelberg Pharma AG

Locations

Charite University Hospital - Campus Virchow Klinikum

Berlin, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Otto-Meyerhof-Zentrum Tagesklinik

Heidelberg, , Germany

Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg

Magdeburg, , Germany

Johannes Gutenberg University

Mainz, , Germany

III Medizinische Klinik Mannheim

Mannheim, , Germany

Klinikum der Universitaet Muenchen - Grosshadern Campus

Munich, , Germany

Klinikum Rechts Der Isar - Technische Universitaet Muenchen

Munich, , Germany

Hospital Muenchen Bogenhausen

Munich, , Germany

Szent Laszlo Korhaz

Budapest, , Hungary

Debreceni Egyetem Onkologiai Tanzek

Debrecen, , Hungary

Petz Aladar County Hospital

Gydr, , Hungary

University of Pecs Faculty of Medicine

Pécs, , Hungary

Szeged University

Szeged, , Hungary

Centro di Riferimento Oncologico - Aviano

Aviano, , Italy

Presidio Ospedaliero di Livorno

Livorno, , Italy

Azienda Ospedaliera di Rilievo Nazionale A.Cardarelli

Naples, , Italy

Istituto Tumori/Fondazione Pascale

Naples, , Italy

Ospedale San Filippo Neri

Rome, , Italy

Altai Oncology Center

Barnaul, , Russia

Moscow Oncology Hospital

Moscow, , Russia

Russian Academy of Medical Sciences Cancer Research Center

Moscow, , Russia

Central Clinical Hospital of the President of the Russian Federation

Moscow, , Russia

Rostov Research Institute of Oncology - Omsk

Omsk, , Russia

Pavlov State Medical University

Saint Petersburg, , Russia

Saint Petersburg State Medical University

Saint Petersburg, , Russia

Hospital de la Santa Cruz i Sant Pau

Barcelona, , Spain

Vall d'Hebron University Hospital

Barcelona, , Spain

Hospital Universitario de Elche

Elche, , Spain

Hospital Virgen de las Nieves

Granada, , Spain

Centro Oncologico M.D. Anderson International Espana

Madrid, , Spain

Cherkassy Regional Oncology Center

Cherkassy, , Ukraine

Bukovinian State Medical University

Chernivtsy, , Ukraine

Dnipropetrovsk State Medical Academy

Dnipropetrovsk, , Ukraine

Donetsk Regional Antitumor Center

Donetsk, , Ukraine

Ivano-Frankovsk Regional Oncology Center

Ivano-Frankivsk, , Ukraine

Grigoriev Institute for Radiology Academy of Medical Science of Ukraine

Kharkiv, , Ukraine

Institute of Oncology

Kiev, , Ukraine

Ukrainian Medical Stomatological Academy

Poltava, , Ukraine

Countries

Germany; Hungary; Italy; Russia; Spain; Ukraine

Other Identifiers

WILEX-WX-60-004

Identifier Type: -

Identifier Source: secondary_id

CDR0000553460

Identifier Type: -

Identifier Source: org_study_id