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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Wilex
ClinicalTrials.gov Identifier:
NCT00499265
First received: July 10, 2007
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Pancreatic Cancer
Drug: gemcitabine hydrochloride
Drug: Serine Proteinase Inhibitor WX-671
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Wilex:

Primary Outcome Measures:
  • Efficacy, in terms of response rate, progression-free survival, time to first metastasis, overall survival, and tumor and uPA system-related markers [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Safety, in terms of vital signs, ECG, biochemistry, hematology (including coagulation), and adverse events [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 95
Study Start Date: April 2007
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: GEMZAR
Experimental: Gemcitabine plus 200 mg WX-671 Drug: Serine Proteinase Inhibitor WX-671
oral, daily
Other Name: MESUPRON
Experimental: Gemcitabine plus 400 mg WX-671 Drug: Serine Proteinase Inhibitor WX-671
oral, daily
Other Name: MESUPRON

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00499265

  Show 39 Study Locations
Sponsors and Collaborators
Wilex
Investigators
Study Chair: Carola Mala, PhD Wilex
  More Information

Additional Information:
No publications provided

Responsible Party: Wilex
ClinicalTrials.gov Identifier: NCT00499265     History of Changes
Other Study ID Numbers: CDR0000553460, WILEX-WX-60-004
Study First Received: July 10, 2007
Last Updated: March 28, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Spain: Ministry of Health
Ukraine: Ministry of Health

Keywords provided by Wilex:
recurrent pancreatic cancer
stage III pancreatic cancer
adenocarcinoma of the pancreas

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Gemcitabine
Protease Inhibitors
Serine Proteinase Inhibitors
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014