Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Docetaxel, Bevacizumab, Thalidomide, and Prednisone in Treating Patients With Metastatic Androgen-Independent Prostate Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Active	18 and over	NCI	NCI-04-C-0257 NCT00091364

Special Category: NIH Clinical Center trial, NCI Web site featured trial

Objectives

Primary

1. Determine prostate-specific antigen response in patients with metastatic androgen-independent adenocarcinoma of the prostate treated with docetaxel, bevacizumab, thalidomide, and prednisone.
2. Determine if docetaxel and bevacizumab cause immunologic changes that would not be compatible with concurrent therapeutic vaccination. (Expansion cohort)

Secondary

1. Determine the time to disease progression and survival duration in patients treated with this regimen.
2. Compare patients with prostate-specific antigen (PSA) elevation only with patients who have both PSA elevation and clinical or radiographic progression.
3. Determine the pharmacokinetics of both docetaxel and thalidomide in patients treated with this regimen.
4. Correlate plasma concentrations of docetaxel and thalidomide with clinical activity or toxicity of these drugs in these patients.
5. Determine the existence and quantification of circulating endothelial cells before and after treatment with this regimen in these patients.
6. Determine the patients' genotype, in terms of cytochrome P450 2C19 polymorphism, and correlate genotype with pharmacokinetics and efficacy of this regimen in these patients.
7. Determine the usefulness of dynamic MRI to monitor the progression of bony and soft tissue disease in patients treated with this regimen.
8. Determine whether there are changes in the molecular markers of angiogenesis (including, but not limited to, serum and urine vascular endothelial growth factor) before and after treatment with this regimen in these patients.
9. Determine the toxicity profile of this regimen in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed androgen-independent adenocarcinoma of the prostate
  • Metastatic disease



• Clinically progressive disease during gonadotrophin-releasing hormone (GnRH) agonist therapy OR after bilateral surgical castration*, as documented by at least 1 of the following parameters:
  • Two consecutively rising prostate-specific antigen (PSA) levels
    • The first rising PSA must be ≥ 1 week from a reference value
    • Patients receiving antiandrogen agents must demonstrate a continued rise in PSA 4 weeks after stopping flutamide and 6 weeks after stopping bicalutamide or nilutamide
  • At least 1 new lesion on bone scan
  • Progressive measurable disease

   [Note: *Patients who have not undergone bilateral surgical castration must continue on GnRH agonist therapy and be maintained on luteinizing hormone-releasing hormone therapy during study participation]




• PSA ≥ 5 ng/mL



• No clinical signs or symptoms of brain and/or leptomeningeal metastases by CT scan or MRI brain scan

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for metastatic prostate cancer

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• Recovered from prior radiotherapy

Surgery

• See Disease Characteristics
• Recovered from prior surgery

Other

• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent therapeutic anticoagulation with warfarin, heparin, or heparinoids
• No other concurrent investigational agents

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• More than 3 months

Hematopoietic

• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8.0 g/dL (transfusion allowed)

Hepatic

• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine ≤ 1.5 times ULN

  OR

• Creatinine clearance ≥ 40 mL/min
• No proteinuria as demonstrated by a urine protein: creatinine ratio ≥ 1.0 if urine dipstick is ≥ 1+
  • If urine analysis shows urine protein: creatinine ratio > 0.5, 24-hour urine should be < 1000 mg

Cardiovascular

• No New York Heart Association class II-IV symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• No persistent systolic blood pressure ≥ 170 mm Hg OR diastolic blood pressure ≥ 100 mm Hg
• No myocardial infarction within the past 6 months
• No transient ischemic attacks or cerebrovascular accident within the past 2 years

Other

• Fertile patients must use effective contraception during and for 2 months after study participation
• Able to ingest oral medication
• No active or ongoing infection
• No peripheral neuropathy > grade 2
• No history of allergic reaction to study drugs or related products
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No other active malignancy within the past 2 years except nonmelanoma skin cancer and superficial bladder carcinoma

Expected Enrollment

A total of 33-60 patients will be accrued for this study within 20 months.

Outcomes

Prostate-specific antigen response
Immunologic changes affecting compatibility of concurrent therapeutic vaccination assessed by regulatory T-cell percentage and function, lymphocyte function, myeloid suppressor cells, and mixed lymphocyte reaction (Expansion cohort)

Pharmacokinetics
Correlation of genotype with efficacy
Circulating endothelial cells in blood at baseline and after completion of study treatment
Tolerability
Time to disease progression
Survival

Outline

This is an open-label study. Some patients will be enrolled in an expansion cohort to study the effects of docetaxel and bevacizumab on the immune system.

Patients receive docetaxel IV over 1 hour and bevacizumab IV over 30-90 minutes on day 1 and oral thalidomide once daily and oral prednisone once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients enrolled in an expansion cohort receive docetaxel IV over 1 hour and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicities. Beginning in course 3 patients also receive oral thalidomide once daily and oral prednisone once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood and tissue sample collection periodically for genotyping, polymorphism, pharmacokinetic, and molecular studies. Patients enrolled in the expansion cohort also undergo blood sample collection for immune cellular, molecular, and angiogenesis marker studies.

After completion of study treatment, patients will be followed approximately annually.

Aragon-Ching JB, Ning YM, Chen CC, et al.: Higher incidence of Osteonecrosis of the Jaw (ONJ) in patients with metastatic castration resistant prostate cancer treated with anti-angiogenic agents. Cancer Invest 27 (2): 221-6, 2009.[PUBMED Abstract]

Ning YM, Retter AS, Latham L, et al.: A phase II trial of docetaxel, thalidomide, bevacizumab, and prednisone in patients (pts) with metastatic androgen-independent prostate cancer (AIPC). [Abstract] 2006 Prostate Cancer Symposium, February 24-26, 2006, San Francisco, CA. A-224, 2006.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Yang-Min Ning, MD, Protocol chair		Ph: 301-796-2321 Email: yn29g@nih.gov

U.S.A.
Maryland
	Bethesda
	NCI - Center for Cancer Research
		Clinical Trials Office - NCI - Center for Cancer Research	Ph:  888-624-1937
	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Featured trial article
Web site for additional information

Registry Information
Official Title		A Phase II Trial of Docetaxel, Thalidomide, Prednisone and Bevacizumab in Patients with Androgen-Independent Prostate Cancer
Trial Start Date		2005-04-17
Trial Completion Date		2009-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00091364
Date Submitted to PDQ		2004-08-12
Information Last Verified		2009-06-30

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