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Study Summary
No. 2009-0291:.......Kidney......Eric Jonasch......Genitourinary Medical Oncology
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Study Summary Title
Study Summary
Number:
2009-0291
Study Title:Randomized, Double-Blind Phase 2 Study of Axitinib (AG-013736) with or without Dose Titration in Patients with Metastatic Renal Cell Carcinoma.
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Physician New Patient Referral
Name:Eric JonaschPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:Genitourinary Medical OncologyReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-2830
Contact us about clinical trials
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General Information
Disease Group:KidneySupported By:Pfizer
Phase of Study:Phase IIReturn
Visit:
Participants must return to clinic on Days 4 & 15 of Cycle 1, and then on Day 1
of each subsequent cycle.
Treatment
Agents:
AG-013736Home Care:Participants will be required to self-administer the study drug and monitor
blood pressure at home.
Treatment Loc:Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimated
Length of Stay
in Houston:
n/a
Description/
Intervention:
The goal of this clinical research study is to compare the effects of different
doses of AG-013736 (Axitinib) in patients with kidney cancer. Researchers also
want to learn about the effects of axitinib on your blood pressure and the
safety of the drug.
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Study Objectives / Outcomes
Primary Objective
To compare the objective response rate (ORR) in patients receiving axitinib with or without dose titration (Arms A and B).

Secondary Objectives
To assess the safety profile, other efficacy parameters, pharmacokinetics, biomarker and/or gene expression profiling correlations with clinical outcome and/or blood pressure (BP) measurements in patients receiving axitinib with or without dose titration (Arms A and B). Although the main study comparison is between Arms A and B, additional information such as those related to safety and biomarker/gene expression profiling correlations with clinical outcome will also be assessed in the non-randomized group, Arm C.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:11/09/2009
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Closed
Projected Accrual:200
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Histologically confirmed mRCC with a component of clear cell histology.

2) No prior systemic therapy for mRCC (including no prior adjuvant or neoadjuvant therapy)

3) If patient has had prior radiation therapy or surgery, then at least 1 week has elapsed since the end of prior radiotherapy; at least 4 weeks since major surgery. All prior treatment-related toxicity must be resolved to NCI CTCAE Version 3.0 grade </= 1 or to baseline, except for alopecia.

4) Presence of measurable disease (i.e., >/=1 malignant tumor mass that can be accurately measured in at least 1 dimension >/= 20 mm with conventional computerized tomography [CT] scan or Magnetic Resonance Imaging [MRI], or >/= 10 mm with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm). Bone lesions, ascites, peritoneal carcinomatosis or biliary lesions, pleural or pericardial effusions, lymphangitic spread to the skin or lung, cystic lesions, or irradiated lesions are not considered measurable. measurable lesion that has not been irradiated

5) (#4 Cont'd) Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one

6) No uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart: the baseline systolic blood pressure readings must be </= 140 mm Hg, and the baseline diastolic blood pressure readings must be </= 90 mm Hg

7) Adequate organ function as defined by the following criteria: a) Absolute neutrophil count (ANC) >/= 1,500 cells/mm^3; b) Platelets >/= 75,000 cells/mm^3; c) Hemoglobin >/= 9.0 g/d; d) AST and ALT </= 2.5 x upper limit of normal (ULN), unless there are liver metastases in which case AST and ALT </= 5.0 x ULN; e) Total bilirubin </= 1.5 x ULN; f) Serum creatinine </= 1.5 x ULN or calculated creatinine clearance >/= 60 mL/min; g) Urinary protein < 2+ by urine dipstick. If dipstick is >/= 2+, then a 24-hour urine protein should be done and results must show protein < 2 g per 24 hours.

8) Male or female, age >/= 18 years.

9) ECOG performance status of 0 or 1.

10) Life expectancy of >/= 12 weeks.

11) Female patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter (or up to 6 months, if required by local regulations). All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within the 72 hours prior to starting treatment.

12) (# 11 cont'd) Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter (or up to 6 months, if required by local regulations). The definition of effective contraception should be in agreement with local regulation and based on the judgment of the principal investigator or a designated associate. Breastfeeding women are not eligible for the study.

13) Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.

14) Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:1) Concurrent use of more than 2 anti-hypertensive medications.

2) Prior use of axitinib (AG-013736).

3) Gastrointestinal abnormalities such as inability to take oral medication; requirement for intravenous alimentation; prior surgical procedures affecting absorption including total gastric resection; treatment for active peptic ulcer disease in the past 6 months; active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy; malabsorption syndromes.

4) Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine).

5) Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort).

6) Ongoing or recent (within 10 days prior treatment start) need for full therapeutic dose of oral or parenteral anticoagulant or chronic daily treatment with aspirin (> 325 mg/day) or clopidogrel (> 75mg/day)

7) Seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.

8) Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism

9) Active bacterial, fungal or viral infection; known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.

10) History of a malignancy (other than renal cell cancer) except those treated with curative intent for non-melanoma skin cancer, in situ breast or in situ cervical cancer, or those treated with curative intent for any other cancer with no evidence of disease for 2 years.

11) Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.

12) Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.

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Links
Registration Number: NCT00835978
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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