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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


Phase 2
18 Years
N/A
Not Enrolling
Both
Pancreatic Cancer

Thank you

Trial Information

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


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.

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

- 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).

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Efficacy, in terms of response rate, progression-free survival, time to first metastasis, overall survival, and tumor and uPA system-related markers

Outcome Time Frame:

3 years

Safety Issue:

No

Principal Investigator

Carola Mala, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Wilex

Authority:

Germany: Federal Institute for Drugs and Medical Devices

Study ID:

CDR0000553460

NCT ID:

NCT00499265

Start Date:

April 2007

Completion Date:

May 2010

Related Keywords:

  • Pancreatic Cancer
  • recurrent pancreatic cancer
  • stage III pancreatic cancer
  • adenocarcinoma of the pancreas
  • Pancreatic Neoplasms

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