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

Pancreatic Cancer Clinical Trial

Official title:

A Randomized, Open Label, Phase II Proof of Concept Study of WX-671 in Combination With Gemcitabine vs.Gemcitabine Alone in Patients With Locally Advanced, Non Resectable Pancreatic Cancer in Order to Evaluate the Anti-Tumor Activity of the Combination Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00499265
• Other study ID #: CDR0000553460
• Secondary ID: WILEX-WX-60-004
• Status: Completed
• Phase: Phase 2
• First received: July 10, 2007
• Last updated: March 28, 2012
• Start date: April 2007
• Est. completion date: May 2010

Study information

• Verified date: March 2012
• Source: Wilex
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyItaly: Ministry of HealthRussia: Ministry of Health of the Russian FederationSpain: Ministry of HealthUkraine: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: May 2010
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

• 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)

PRIOR CONCURRENT THERAPY:

• 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).

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• gemcitabine hydrochloride
1000 mg/m2 as 30 min i.v. infusion once weekly for 7/8 weeks and then every 3/4 weeks
• Serine Proteinase Inhibitor WX-671
oral, daily
• Serine Proteinase Inhibitor WX-671
oral, daily

Locations

Country	Name	City	State
Germany	Charite University Hospital - Campus Virchow Klinikum	Berlin
Germany	Universitaetsklinikum Freiburg	Freiburg
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	Hospital Muenchen Bogenhausen	Munich
Germany	Klinikum der Universitaet Muenchen - Grosshadern Campus	Munich
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Hungary	Szent Laszlo Korhaz	Budapest
Hungary	Debreceni Egyetem Onkologiai Tanzek	Debrecen
Hungary	Petz Aladar County Hospital	Gydr
Hungary	University of Pecs Faculty of Medicine	Pecs
Hungary	Szeged University	Szeged
Italy	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
Russian Federation	Altai Oncology Center	Barnaul
Russian Federation	Central Clinical Hospital of the President of the Russian Federation	Moscow
Russian Federation	Moscow Oncology Hospital	Moscow
Russian Federation	Russian Academy of Medical Sciences Cancer Research Center	Moscow
Russian Federation	Rostov Research Institute of Oncology - Omsk	Omsk
Russian Federation	Saint Petersburg State Medical University	Saint Petersburg
Russian Federation	Pavlov State Medical University	St. Petersburg
Spain	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
Ukraine	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-Frankovsk
Ukraine	Grigoriev Institute for Radiology Academy of Medical Science of Ukraine	Kharkiv
Ukraine	Institute of Oncology	Kiev
Ukraine	Ukrainian Medical Stomatological Academy	Poltava

Sponsors (1)

Lead Sponsor	Collaborator
Wilex

Countries where clinical trial is conducted

Germany,  Hungary,  Italy,  Russian Federation,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy, in terms of response rate, progression-free survival, time to first metastasis, overall survival, and tumor and uPA system-related markers		3 years	No
Primary	Safety, in terms of vital signs, ECG, biochemistry, hematology (including coagulation), and adverse events		3 years	Yes