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Study Summary
No. 2003-0982:.......Kidney......Eric Jonasch......Genitourinary Medical Oncology
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Study Summary Title
Study Summary
Number:
2003-0982
Study Title:A Phase II Neoadjuvant Clinical Trial to Evaluate the Efficacy of Recombinant Humanized Monoclonal Anti-VEGF Antibody rhuMab VEGF (Bevacizumab) for 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:N/A
Phase of Study:Phase IIReturn
Visit:
Patients visit MDACC every 2 weeks, +/- 2 days (i.e., at the beginning of each
new treatment cycle).
Treatment
Agents:
BevacizumabHome Care:N/A
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
N/A
Description/
Intervention:
The goal of this clinical research study is to learn if bevacizumab (AvastinŽ)
can control metastatic renal cell carcinoma. The safety of the treatment will
also be studied.
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Study Objectives / Outcomes
Primary:
1. To assess the efficacy of neoadjuvant therapy of bevacizumab by evaluating time to progression.
2. Toxicities of therapy with bevacizumab in RCC.

Secondary:
Clinical:
1. Response rate
2. Duration of response
3. Overall Survival

Preclinical:
1. Serum and plasma levels of MMP-9 and MMP-2, IL-6, VEGF, and bFGF pre- and post- therapy (optional studies).
2. Tissue expression of Phospho-EGFR, VEGF, vessel count CD31/34, AKT and Phospho-AKT, MAPK, TGF-alpha, phospho-STAT3 and TUNEL post therapy (optional studies).
3. cDNA microarray analysis of tissue post-therapy (optional studies).
4. Tissue expression of tumor infiltrating lymphocytes and tumor antigens
5. Pathological response rate in primary tumor.
6. To evaluate the Single Nucleothide Polymorphisms (SNP) patterns in nephrectomy specimens from patients participating in the study.
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Study Status Information
Study Activation / Registration Date:02/22/2005
IRB Review and Approval Date:01/21/2004
Study Type:Therapeutic
Recruitment Status:Closed
Projected Accrual:N/A
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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) Patients with histologically or cytologically confirmed clear cell metastatic RCC who are eligible for cytoreductive nephrectomy.

2) Patients must have measurable disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures greater than or equal to 20 mm with conventional techniques or greater than or equal to 10 mm with spiral CT scan. This does not include primary tumors, which will be removed.

3) ECOG performance status less than or equal to 1

4) Female patients of childbearing potential (i.e. premenopausal, no hysterectomy) must have a normal plasma beta human chorionic gonadotropin (bHCG) within 24 hours prior to enrolling in the study due to the possible teratogenic effect. Patients with an elevated bHCG will undergo appropriate evaluation to rule out pregnancy (i.e. referral to Gyn service, pelvic ultrasound) and if pregnancy is ruled out and elevated bHCG is determined to be of tumor origin, patients will be permitted to proceed on study.

5) Patients of child fathering or childbearing potential must agree to practice a form of medically acceptable birth control while on study, i.e. condoms.

6) Patients must give written informed consent prior to initiation of therapy, in keeping with the policies of the institution. Patients with a history of major psychiatric illness must be judged able to fully understand the investigational nature of the study and the risks associated with the therapy. The only approved consent is attached to this protocol.

7) Patients must have ability to comply with study and/or follow-up procedures.

8) Patients must have adequate organ and marrow function within 14 days as defined below: absolute neutrophil count >/=1,500/micro platelets >/= 75,000/micro Hgb > 9.0 g/dL (may be transfused or receive epoetin alfa permitted) total bilirubin </= 2.0 mg/dL albumin > 3.0 g/dL serum creatinine </= 2.0 mg/dL AST(SGOT) and/or ALT (SGPT) </= 2.5 X ULN, no liver metastases AST(SGOT) and/or ALT (SGPT) </= 5 X ULN, liver metastases present.

Exclusion Criteria:1) Patients must not have organ allografts.

2) Patients must not have had major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study (other than defined by protocol); or fine needle aspirations or core biopsies within 7 days prior to Day 0.

3) No prior malignancy is allowed, except for non-melanoma skin cancer, in situ carcinoma of any site, or other cancers for which the patient has been adequately treated and disease free for 5 years.

4) Patients must not have received any systemic anticancer therapy. Radiation therapy is allowed if >/= 2 weeks from study drug administration.

5) Patients must not be scheduled to receive another experimental drug while on this study. Patients are permitted to be on concomitant bisphosphonates and megestrol acetate.

6) Patients must not have a primary brain tumor (excluding meningiomas other benign lesions), any brain metastases, leptomeningeal disease, seizure disorders not controlled with standard medical therapy, or history of stroke within the past 5 years.

7) History of serious systemic disease, including myocardial infarction or unstable angina within the last 12 months, history of hypertensive crisis or hypertensive encephalopathy, uncontrolled hypertension (blood pressure of >140/90 mmHg on medication), New York Heart Association (NYHA) Grade II or greater congestive heart failure, unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), significant vascular disease or symptomatic peripheral vascular disease.

8) Patients must not have history of other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.

9) Patients receiving any concomitant systemic therapy for renal cell cancer are excluded, but patients taking bisphosphonates and megestrol acetate are not excluded.

10) Patients must not require total parenteral nutrition with lipids.

11) Patients must not have significant proteinuria at baseline. Patients who are unexpectedly discovered to have greater than or equal to 1+ proteinuria on routine urinalysis at baseline should undergo a 24 hour urine collection, which must be an adequate collection and must demonstrate less than or equal to 1g of protein/24 hr to allow participation in the study.

12) Patients must not have clinical history of coagulopathy, bleeding diathesis or thrombosis.

13) Patients must not have a serious, nonhealing wound, ulcer, or bone fracture.

14) Pregnancy (positive pregnancy test) or lactation.

15) History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.

16) Know hypersensitivity to any component of bevacizumab.

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Links
Registration Number: NCT00113217
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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