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

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00091364

Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die.

Bevacizumab and thalidomide may stop the growth of prostate cancer by stopping blood flow to the tumor. Combining docetaxel, bevacizumab, and thalidomide with prednisone may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving docetaxel, bevacizumab, and thalidomide together with prednisone works in treating patients with metastatic prostate cancer.

Condition	Intervention	Phase
Prostate Cancer	Biological: bevacizumab Drug: docetaxel Drug: prednisone Drug: thalidomide Genetic: polymorphism analysis Other: immunoenzyme technique Other: laboratory biomarker analysis Other: pharmacological study	Phase II

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Thalidomide Prednisone Docetaxel Bevacizumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Trial of Docetaxel, Thalidomide, Prednisone and Bevacizumab in Patients With Androgen-Independent Prostate Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Prostate-specific antigen response [ Designated as safety issue: No ]
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) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetics [ Designated as safety issue: No ]
Correlation of genotype with efficacy [ Designated as safety issue: No ]
Circulating endothelial cells in blood at baseline and after completion of study treatment [ Designated as safety issue: No ]
Tolerability [ Designated as safety issue: Yes ]
Time to disease progression [ Designated as safety issue: No ]
Survival [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	April 2005
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

Secondary

Determine the time to disease progression and survival duration in patients treated with this regimen.
Compare patients with prostate-specific antigen (PSA) elevation only with patients who have both PSA elevation and clinical or radiographic progression.
Determine the pharmacokinetics of both docetaxel and thalidomide in patients treated with this regimen.
Correlate plasma concentrations of docetaxel and thalidomide with clinical activity or toxicity of these drugs in these patients.
Determine the existence and quantification of circulating endothelial cells before and after treatment with this regimen in these patients.
Determine the patients' genotype, in terms of cytochrome P450 2C19 polymorphism, and correlate genotype with pharmacokinetics and efficacy of this regimen in these patients.
Determine the usefulness of dynamic MRI to monitor the progression of bony and soft tissue disease in patients treated with this regimen.
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.
Determine the toxicity profile of this regimen in these patients.

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.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

More than 3 months

Hematopoietic

WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00091364

Locations

United States, Maryland
NCI - Center for Cancer Research	Recruiting
Bethesda, Maryland, United States, 20892
Contact: Clinical Trials Office - NCI - Center for Cancer Research 888-624-1937
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Yang-Min Ning, MD

NCI - Medical Oncology Branch

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

Web site for additional information This link exits the ClinicalTrials.gov site

Publications:

Aragon-Ching JB, Ning YM, Chen CC, Latham L, Guadagnini JP, Gulley JL, Arlen PM, Wright JJ, Parnes H, Figg WD, Dahut WL. Higher incidence of Osteonecrosis of the Jaw (ONJ) in patients with metastatic castration resistant prostate cancer treated with anti-angiogenic agents. Cancer Invest. 2009 Feb;27(2):221-6.

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.

Responsible Party:	NCI - Center for Cancer Research ( William Dahut )
Study ID Numbers:	CDR0000387837, NCI-04-C-0257
Study First Received:	September 7, 2004
Last Updated:	April 22, 2009
ClinicalTrials.gov Identifier:	NCT00091364 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the prostate
recurrent prostate cancer
stage IV prostate cancer

Study placed in the following topic categories:

Anti-Inflammatory Agents
Prednisone
Immunologic Factors
Antineoplastic Agents, Hormonal
Genital Neoplasms, Male
Prostatic Diseases
Thalidomide
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Urogenital Neoplasms
Bevacizumab

Genital Diseases, Male
Angiogenesis Inhibitors
Immunosuppressive Agents
Hormones
Glucocorticoids
Recurrence
Docetaxel
Anti-Bacterial Agents
Adenocarcinoma
Prostatic Neoplasms
Androgens

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Prednisone
Anti-Infective Agents
Thalidomide
Prostatic Diseases
Genital Neoplasms, Male
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Urogenital Neoplasms
Bevacizumab
Hormones
Docetaxel
Anti-Bacterial Agents

Neoplasms by Site
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents, Hormonal
Growth Substances
Genital Diseases, Male
Angiogenesis Inhibitors
Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Prostatic Neoplasms
Leprostatic Agents

ClinicalTrials.gov processed this record on May 06, 2009