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A randomized phase 2 study of the anti-angiogenesis agent AG-013736 in combination with gemcitabine in patients with chemotherapy-naïve advanced pancreatic cancer preceded by a phase 1 portio

Conditions
Treatment of patients with chemotherapy-naïve, locally advanced or metastatic epithelial cancer of the exocrine pancreas
MedDRA version: 5.1Level: LLTClassification code 10033604
Registration Number
EUCTR2005-000053-30-DE
Lead Sponsor
Pfizer Pharma GmbH
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
102
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 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 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 <2+
8. no evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart on the same day (The baseline systolic blood pressure readings must be less than or equal to 140 mm Hg, and the baseline diastolic blood pressure readings must be less than or equal to 90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible)
9. ECOG performance status of 0, 1, or 2 (See Appendix 1)
10. life expectancy = 12 weeks
11. adults =18 years of age
12. negative serum or urine pregnancy test for women of child-bearing potential
13. evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the trialpatients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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. brain metastases (baseline CT or MRI of brain required only if clinically indicated)
6. inability to take oral medications
7. history of hemorrhagic or thrombotic cerebrovascular event in the past 12 months
8. major surgical procedure within 4 weeks of randomization for Phase 2
9. unstable or severe intercurrent medical condition that, in the opinion of the investigator, might interfere with achievement of study objectives
10. psychological or sociological conditions, addictive disorders, or family problems, which would preclude compliance with the protocol
11. 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
12. patients having procreative potential who are not using adequate contraception or practicing abstinence
13. women who are pregnant or breast-feeding
14. 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.
15. 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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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