Clinical trial NCT00499265 (phase 2, status: completed)
Conditions: pancreatic cancer
ICD codes: C25.3
Drugs: gemcitabine hydrochloride, serine proteinase inhibitor wx-671, serine proteinase inhibitor wx-671
SMILES: NC1=NC(=O)N(C=C1)[C@@H]1O[C@H](CO)[C@@H](O)C1(F)F, CCOC(=O)N1CCN(CC1)C(=O)[C@H](CC1=CC=CC(=C1)C(\N)=N/O)NS(=O)(=O)C1=C(C=C(C=C1C(C)C)C(C)C)C(C)C, CCOC(=O)N1CCN(CC1)C(=O)[C@H](CC1=CC=CC(=C1)C(\N)=N/O)NS(=O)(=O)C1=C(C=C(C=C1C(C)C)C(C)C)C(C)C
Eligibility 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).