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Docetaxel, Thalidomide, Prednisone, and Bevacizumab to Treat Metastatic Prostate Cancer

Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Prostatic Neoplasms

Intervention: Docetaxel (Drug); Thalidomide (Drug); Prednisone (Drug); bevacizumab (Biological); polymorphism analysis (Genetic); immunoenzyme technique (Other); laboratory biomarker analysis (Other); pharmacological study (Other)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
William L Dahut, M.D., Principal Investigator, Affiliation: National Cancer Institute (NCI)

Summary

This is a Phase II study of docetaxel, bevacizumab, prednisone and thalidomide in patients with androgen independent metastatic prostate cancer who are previously untreated with chemotherapy. The primary objective of this study is to determine if the combination of docetaxel, thalidomide and bevacizumab is able to be associated with a sufficiently high proportion of patients with a prostate-specific antigen (PSA) response to be worthy of further investigation in metastatic prostate cancer. We will also be looking at multiple secondary endpoints. These will include possible pharmacokinetic interactions among the study agents, potential correlation between patient genotype and efficacy of treatment. We will also be looking for circulating tumor cells in blood before and after treatment. Additionally we will be monitoring the tolerability of the regimen and survival duration as endpoints as well. We hope to use this trial to build on the promising results seen in our thalidomide/docetaxel protocol where there was a significant PSA decline and a trend toward survival benefit.

Clinical Details

Official title: A Phase II Trial of Docetaxel, Thalidomide, Prednisone and Bevacizumab in Patients With Androgen-Independent Prostate Cancer

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Number of Participants Who Had a Prostate-specific Antigen (PSA) Response

Immune Response

Secondary outcome: Number of Participants With Adverse Events

Detailed description: This is a Phase II study of docetaxel, bevacizumab, prednisone and thalidomide in patients with androgen independent metastatic prostate cancer who are previously untreated with chemotherapy. The primary objective of this study is to determine if the combination of docetaxel, thalidomide and bevacizumab is able to be associated with a sufficiently high proportion of patients with a PSA response to be worthy of further investigation in metastatic prostate cancer. We will also be looking at multiple secondary endpoints. These will include possible pharmacokinetic interactions among the study agents, potential correlation between patient genotype and efficacy of treatment. We will also be looking for circulating endothelial cells in blood before and after treatment. Additionally we will be monitoring the tolerability of the regimen, time to disease progression, and survival duration as endpoints as well. We hope to use this trial to build on the promising results seen in our thalidomide/docetaxel protocol where there was a significant PSA decline and a trend toward survival benefit.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

- INCLUSION CRITERIA:

Androgen-independent metastatic adenocarcinoma of the prostate defined as progressive metastatic disease while on gonadotropin releasing hormone (GnRH) agonists or post surgical castration Histopathological documentation of prostate cancer confirmed in the National Cancer Institute (NCI) Laboratory of Pathology at the National Institutes of Health, the Pathology Department at Walter Reed Medical Center or the Pathology Department at National Naval Medical Center, prior to starting this study. In addition, patients whose slides are lost or unavailable will be eligible for the study if they provide documentation of prostate cancer and if they meet criteria of clinically progressive prostate cancer as outlined in section 3. 1.1. 3. Clinically progressive prostate cancer documented prior to entry. Progression must be documented by at least one of the following parameters:

- Two consecutively rising prostate-specific antigen (PSA) levels. The first rising

PSA must be a minimum of one week from a reference value. It is recognized that PSA fluctuations are such that the confirmatory PSA value might be less than the previous one. In these cases, that patient would still be eligible provided the next PSA was greater than the first rising PSA value. Patients must have PSA greater than or equal to 5. 0.

- At least one new lesion on bone scan.

- Progressive measurable disease.

Patients must have undergone bilateral surgical castration or must continue on GNRH agonist. Those patients receiving an anti-androgen agent and are entering the trial due to a rise in PSA must demonstrate a continued rise in PSA 4 weeks after stopping flutamide and 6 weeks after stopping bicalutamide or nilutamide. Patients may not have received any chemotherapy for metastatic prostate cancer Age greater than or equal to 18 years Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 Life expectancy of greater than 3 months Patients must have adequate organ and marrow function as defined below: Leukocytes- greater than or equal to 3,000/microliter Absolute neutrophil count- greater than or equal to 1,500/microliter Platelets- greater than or equal to 100,000/microliter

Hemoglobin- greater than or equal to 8. 0g/L - transfusions acceptable

Total bilirubin- less than or equal to 1. 5 times the institutional upper limits of normal Aspartate aminotransferase (AST)serum glutamic oxaloacetic transaminase(SGOT) and alanine

aminotransferase (ALT)serum glutamic pyruvic transaminase(SGPT) - less than or equal to

2. 5 times the institutional upper limits of normal Creatinine or Creatinine clearance- less than or equal to 1. 5 times the institutional upper limits of normal or greater than or equal to 40 mL/min/1. 73 m^2 for patients with creatinine levels above institutional normal. Recovered from any toxicity from surgery or radiotherapy Must be willing to travel from their home to the National Institutes of Health (NIH) for follow-up visits Able and willing to follow instructions and conform to protocol. Patients may have had no other active malignancy within the past 2 years with the exception of non-melanoma skin cancer and superficial bladder carcinoma No history of myocardial infarction within the past 6 months, uncontrolled congestive heart failure (CHF) or uncontrolled angina pectoris Patients must agree to use adequate contraception (abstinence; hormonal or barrier method of birth control) for the study and at least 2 months after completion. Ability to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: Present clinical signs or symptoms of brain and/or leptomeningeal metastases confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) brain scan. Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (American Heart Association (AHA) Class II or worse), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Persistent systolic blood pressure greater than or equal to 170 mmHg or diastolic blood pressure greater than or equal to 100 mmHg. Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with docetaxel, bevacizumab, and/or the combination. Proteinuria, as demonstrated by a urine, protein, creatinine (UPC) ratio greater than or equal to 1. 0 at screening, required to be assessed if urine dipstick is greater than or equal to 1+. Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio. For UPC ratio > 0. 5, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment. Note: UPC ratio of spot urine is an estimation of the

24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine

protein of 1 gm. UPC ratio is calculated using one of the following formula:

- [urine protein]/[urine creatinine] - if both protein and creatinine are reported in

mg/dL

- [(urine protein) x 0. 088]/[urine creatinine] - if urine creatinine is reported in

mmol/L Therapeutic anticoagulation with coumadin, heparins, or heparinoids. Greater than Grade 2 peripheral neuropathy at baseline. History of transient ischemic attacks (TIA) or cerebrovascular accident (CVA) within the past 2 years. History of allergic reaction to docetaxel, prednisone, thalidomide and/or bevacizumab or related products. Patients who are on concurrent investigational agent(s) Patients who are unable to ingest oral medication. INCLUSION OF WOMEN AND MINORITIES Men of all races and ethnic groups are eligible for this trial. Every effort will be made to recruit minorities in this study. Women are ineligible for this study.

Locations and Contacts

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States
Additional Information

NIH Clinical Center Detailed Web Page

Related publications:

Horwitz SB. Taxol (paclitaxel): mechanisms of action. Ann Oncol. 1994;5 Suppl 6:S3-6. Review.

McDonnell TJ, Troncoso P, Brisbay SM, Logothetis C, Chung LW, Hsieh JT, Tu SM, Campbell ML. Expression of the protooncogene bcl-2 in the prostate and its association with emergence of androgen-independent prostate cancer. Cancer Res. 1992 Dec 15;52(24):6940-4.

Berchem GJ, Bosseler M, Sugars LY, Voeller HJ, Zeitlin S, Gelmann EP. Androgens induce resistance to bcl-2-mediated apoptosis in LNCaP prostate cancer cells. Cancer Res. 1995 Feb 15;55(4):735-8.

Starting date: August 2004
Last updated: March 11, 2015

Page last updated: August 23, 2015

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