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

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

73 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-04-19

Study Completion Date

2018-01-09

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Prostatic Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Main cohort - Prostate Cancer

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.

Group Type EXPERIMENTAL

Docetaxel

Intervention Type DRUG

Docetaxel 75 mg/m\^2 intravenously over 60 minutes on cycle 1 day 1 repeated every 21 days.

Thalidomide

Intervention Type DRUG

Thalidomide 200 mg by mouth daily throughout the cycle.

Prednisone

Intervention Type DRUG

Prednisone 10 mg by mouth daily throughout the cycle.

bevacizumab

Intervention Type BIOLOGICAL

Bevacizumab 15 mg/kg intravenously on cycle 1 day 1 every 21 days.

polymorphism analysis

Intervention Type GENETIC

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.

immunoenzyme technique

Intervention Type OTHER

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.

laboratory biomarker analysis

Intervention Type OTHER

Serum and urine samples will be collected at baseline and monthly to measure VEGF (vascular endothelial growth factor) levels.

pharmacological study

Intervention Type OTHER

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.

Expansion cohort - Prostate Cancer

Docetaxel 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.

Group Type EXPERIMENTAL

Docetaxel

Intervention Type DRUG

Docetaxel 75 mg/m\^2 intravenously over 60 minutes on cycle 1 day 1 repeated every 21 days.

Thalidomide

Intervention Type DRUG

Thalidomide 200 mg by mouth daily throughout the cycle.

Prednisone

Intervention Type DRUG

Prednisone 10 mg by mouth daily throughout the cycle.

bevacizumab

Intervention Type BIOLOGICAL

Bevacizumab 15 mg/kg intravenously on cycle 1 day 1 every 21 days.

Interventions

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Docetaxel

Docetaxel 75 mg/m\^2 intravenously over 60 minutes on cycle 1 day 1 repeated every 21 days.

Intervention Type DRUG

Thalidomide

Thalidomide 200 mg by mouth daily throughout the cycle.

Intervention Type DRUG

Prednisone

Prednisone 10 mg by mouth daily throughout the cycle.

Intervention Type DRUG

bevacizumab

Bevacizumab 15 mg/kg intravenously on cycle 1 day 1 every 21 days.

Intervention Type BIOLOGICAL

polymorphism analysis

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.

Intervention Type GENETIC

immunoenzyme technique

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.

Intervention Type OTHER

laboratory biomarker analysis

Serum and urine samples will be collected at baseline and monthly to measure VEGF (vascular endothelial growth factor) levels.

Intervention Type OTHER

pharmacological study

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.

Intervention Type OTHER

Other Intervention Names

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Taxotere Thalomid Deltasone Avastin

Eligibility Criteria

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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.

Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No