Treatment of patients with chemotherapy-naïve, locally advanced or metastatic epithelial cancer of the exocrine pancreas MedDRA version: 5.1 Level: LLT Classification code 10033604
Conditions
Interventions
Product Name: AG-013736
Product Code: AG-013736
Pharmaceutical Form: Film-coated tablet
CAS Number: 319460-85-0
Current Sponsor code: AG
Sponsors
Pfizer Inc. - La Jolla laboratories
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. patients with advanced (localized but surgically unresectable or metastatic) histologically/cytologically proven epithelial cancer of the exocrine pancreas 2. no prior therapy for metastatic disease 3. no adjuvant chemotherapy within the 4 weeks before registration (Phase 1) or randomization (Phase 2) (patient must have recovered from all treatment-related toxicities and must have evidence of disease progression following adjuvant treatment) 4. no radiotherapy within the 4 weeks before registration (Phase 1) or randomization (Phase 2) (patient must have recovered from all treatment-related toxicities and must have evidence of disease progression following treatment. Prior radiotherapy [with or without fluoropyrimidines for radiosensitization] is allowed provided the patient has disease outside the radiation port) 5. adequate bone marrow function as defined by: - ANC =1500 cells/mm3 - platelets =100, 000 cells/mm3 - hemoglobin =9 g/dL (which may be obtained by transfusion or growth factor support) 6. adequate liver function as defined by: - bilirubin =1.5 times upper limit of normal (x ULN) - AST and ALT =2.5 x ULN 7. adequate renal function as defined by both: - serum creatinine =1.5 x ULN - =500 mg urinary protein/24 hours or dipstick =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. prior treatment with gemcitabine, VEGF/VEGFR inhibitors, or anti-angiogenesis treatment of any kind in the adjuvant setting. 2. patients with locally advanced disease who are candidates for radiation therapy. 3. current use or anticipated need for drugs that are known CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine) during the course of study 4. current use or anticipated need for drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St John’s wort) during the course of study 5. requirement of anticoagulant therapy except for low-dose anticoagulants for maintenance of patency of central venous access or prevention of deep vein thrombosis (DVT) 6. uncontrolled brain metastases (a controlled brain metastasis must be previously treated, asymptomatic, and without growth for 4 months) 7. inability to take oral medications 8. history of hemorrhagic or thrombotic cerebrovascular event in the past 12 months 9. major surgical procedure within 4 weeks of treatment for Phase 1 or randomization for Phase 2 10. unstable or severe intercurrent medical condition that, in the opinion of the investigator, might interfere with achievement of study objectives 11. psychological or sociological conditions, addictive disorders, or family problems, which would preclude compliance with the protocol 12. history of a malignancy (other than pancreatic cancer) except those patients treated with curative intent for skin cancer (other than melanoma) or in situ cervical cancer or those treated with curative intent for any other cancer with no evidence of disease 13. patients having procreative potential who are not using adequate contraception or practicing abstinence 14. women who are pregnant or breast-feeding 15. patients with proteinuria. (Patients with >1+ protein on urine dipstick at baseline should undergo a 24-hour urine collection. Results must demonstrate =500 mg of protein in 24 hours to allow participation in the study. 16. other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with trial participation or investigational product administration or may interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine whether the overall survival of the combination of AG-013736 and gemcitabine is superior to that of gemcitabine alone in patients who have advanced pancreatic cancer that has not been previously treated with systemic therapy.;Primary end point(s): The primary end point is overall survival (Phase 2 portion). All deaths from any cause will be included in the analysis.; Secondary Objective: 1) determine the doses of AG-013736 and gemcitabine that can be safely given together (Phase 1 portion); 2) determine the adverse event profile and dose-limiting toxicities for the combination; 3) assess gemcitabine and AG-013736 pharmacokinetic parameters in the Phase 1 portion of the study, and evaluate population pharmacokinetics of AG-013736 in the Phase 2 portion of the study; 4) document response (Phase 1 portion) and determine the response rate and duration of response (Phase 2 portion) in patients who have measurable disease at baseline; 5) determine progression-free survival and 1-year survival (Phase 2 portion); 6) assess patient-reported outcomes (PROs) of health-related quality of life (HRQoL) and pancreatic cancer-specific symptoms (Phase 2 portion) | — |
Countries
Belgium, Germany, Italy, Spain, United Kingdom
Outcome results
None listed