Docetaxel, Thalidomide, Prednisone, and Bevacizumab to Treat Metastatic Prostate Cancer
A Phase II Trial of Docetaxel, Thalidomide, Prednisone and Bevacizumab in Patients With Androgen-Independent Prostate Cancer
2 other identifiers
interventional
73
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2005
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 6, 2004
CompletedFirst Posted
Study publicly available on registry
August 9, 2004
CompletedStudy Start
First participant enrolled
April 19, 2005
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2011
CompletedResults Posted
Study results publicly available
November 14, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
January 9, 2018
CompletedApril 20, 2018
March 1, 2018
6.7 years
August 6, 2004
October 12, 2012
March 22, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Number of Participants Who Had a Prostate-specific Antigen (PSA) Response
PSA response was assessed by the PSA Consensus Criteria. PSA decline is defined as a decline in PSA of at least 50% with no other evidence of disease progression.
21.6 months
Immune Response
Cellular immune response and cytokines were evaluated after two cycles of therapy in the expansion cohort. Those cycles included treatment with bevacizumab and docetaxel as a pre-medication.
6 weeks
Secondary Outcomes (9)
Number of Participants With Adverse Events
37 months
Time to Progression Using Bubley Criteria
up to 40 months
Disease Progression by Clinical and Radiographic Criteria Without the Use of Prostate-Specific Antigen (PSA)
up to 34 months
Number of Participants Who Died After a Follow Up of 34 Months Following Treatment
34 months
Plasma Concentrations of Docetaxel and Thalidomide and Clinical Activity or Toxicity
Pre-dose on C1D1, 5 minutes before the end of infusion, and 15, and 30 minutes, and 1, 2,4,8, and 24 hours after the end of infusion
- +4 more secondary outcomes
Study Arms (2)
Main cohort - Prostate Cancer
EXPERIMENTALDocetaxel 75 mg/m\^2 intravenously over 60 minutes on cycle 1 day 1 repeated every 21 days. Thalidomide 200 mg by mouth daily throughout the cycle. Prednisone 10 mg by mouth daily throughout the cycle. Bevacizumab 15 mg/kg intravenously on cycle 1 day 1 every 21 days.
Expansion cohort - Prostate Cancer
EXPERIMENTALDocetaxel 75 mg/m\^2 intravenously over 60 minutes and Bevacizumab 15 mg/kg intravenously was given for 2 cycles. After two cycles Prednisone 10 mg by mouth daily and Thalidomide 200 mg by mouth daily was added.
Interventions
Docetaxel 75 mg/m\^2 intravenously over 60 minutes on cycle 1 day 1 repeated every 21 days.
Thalidomide 200 mg by mouth daily throughout the cycle.
Prednisone 10 mg by mouth daily throughout the cycle.
Bevacizumab 15 mg/kg intravenously on cycle 1 day 1 every 21 days.
Two buffy coat tubes (two 7mL blue tiger top tubes) will be obtained and wrapped in foil when the patient enters onto the study. DNA (deoxyribonucleic acid) will be isolated only for the purpose of genotype analysis of enzymes with putative relevance for docetaxel or thalidomide disposition.
The PBMC (peripheral blood mononuclear cells) of patients will be analyzed pre-treatment and post cycle 2 for any changes in the function of regulatory T cells. The following analysis will be performed: flow cytometry analysis, CD4 CD25 T cell enrichment, and immunosuppression assay.
Serum and urine samples will be collected at baseline and monthly to measure VEGF (vascular endothelial growth factor) levels.
Plasma concentrations of docetaxel and thalidomide will be determined to assess interactions between docetaxel (and thalidomide) and the concomitant therapy.The analysis will be performed using a validated method based on liquid chromotography with mass-spectrometric detection.
Eligibility Criteria
You may qualify if:
- 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
- +12 more criteria
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (3)
Horwitz SB. Taxol (paclitaxel): mechanisms of action. Ann Oncol. 1994;5 Suppl 6:S3-6.
PMID: 7865431BACKGROUNDMcDonnell 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.
PMID: 1458483BACKGROUNDBerchem 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.
PMID: 7850782BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Ravi Madan, M.D.
- Organization
- National Cancer Institute, National Institutes of Health
Study Officials
- PRINCIPAL INVESTIGATOR
Ravi Madan, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
August 6, 2004
First Posted
August 9, 2004
Study Start
April 19, 2005
Primary Completion
December 31, 2011
Study Completion
January 9, 2018
Last Updated
April 20, 2018
Results First Posted
November 14, 2012
Record last verified: 2018-03
Data Sharing
- IPD Sharing
- Will not share