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Prostatic NeoplasmsPhase 2NCT00089609

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

A Phase 2 study testing Docetaxel, Thalidomide and Prednisone in people with Prostatic Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostatic Neoplasms
What is being tested?
Docetaxel, Thalidomide and Prednisone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
73 participants
Where
1 siteUnited States
Study dates
19 Apr 2005to 9 Jan 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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.

Who cannot join

  • 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:
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  • [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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Docetaxel, Thalidomide, Prednisone, bevacizumab, polymorphism analysis
Keywords
Hormones, Angiogenesis, Markers, Tumor, Prostate Cancer
Medical subject headings
Prostatic Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DocetaxelDrug

    Also called Taxotere

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

  • ThalidomideDrug

    Also called Thalomid

    Thalidomide 200 mg by mouth daily throughout the cycle.

  • PrednisoneDrug

    Also called Deltasone

    Prednisone 10 mg by mouth daily throughout the cycle.

  • bevacizumabBiological

    Also called Avastin

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

  • polymorphism analysisGenetic

    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 techniqueOther

    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 analysisOther

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

  • pharmacological studyOther

    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.

Study groups in NCT00089609
Study groupRoleWhat they receive
Main cohort - Prostate CancerExperimentalDocetaxel 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.
Receives: Drug: Docetaxel; Drug: Thalidomide; Drug: Prednisone; Biological: bevacizumab; Genetic: polymorphism analysis; Other: immunoenzyme technique; Other: laboratory biomarker analysis; Other: pharmacological study
Expansion cohort - Prostate CancerExperimentalDocetaxel 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.
Receives: Drug: Docetaxel; Drug: Thalidomide; Drug: Prednisone; Biological: bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 21.6 months

  2. 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.

    Measured: 6 weeks

Secondary outcomes (9)

  1. Number of Participants With Adverse Events

    Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

    Measured: 37 months

  2. Time to Progression Using Bubley Criteria

    Time to disease progression was based on the Prostate-Specific Antigen (PSA) Working Group 1 Criteria (Bubley Criteria) and standard Response Evaluation Criteria in Solid Tumors (RECIST) for measurable disease. Per the criteria, investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period.

    Measured: up to 40 months

  3. Disease Progression by Clinical and Radiographic Criteria Without the Use of Prostate-Specific Antigen (PSA)

    Clinical and radiographic response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking s reference the smallest sum LD since the treatment started. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded or the appearance of one or more new lesions.

    Measured: up to 34 months

  4. Number of Participants Who Died After a Follow Up of 34 Months Following Treatment

    From on study date to date of death at 34 months.

    Measured: 34 months

  5. Plasma Concentrations of Docetaxel and Thalidomide and Clinical Activity or Toxicity

    The analysis will be performed using a validated method based on liquid chromatography with mass-spectrometric detection.

    Measured: 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

  6. Number of Participants With a Significant Increase in Circulating Apoptotic Endothelial Cell (CAEC) Level

    The assay utilized has no standard curve. Categorizing patients with ≥ 75% PSA decline in one group and < PSA decline in another group, every patient is their own control with comparison of CAEC at baseline vs. 6 weeks (after two cycles of treatment). Blood is drawn from the patient and a million viable mononuclear cells are counted and then it is determined how many CAECs are in the specimen. The cell count is then compared from baseline to post 2 cycles of treatment. Thus, "significant increase" is dependent upon this comparison and varies between patients.

    Measured: Baseline and at 6 weeks (after two cycles of treatment)

  7. Analyze the Patients Genotype With Regard to Cytochrome P450 2C19 Polymorphism and Correlate That With Pharmacokinetics and Efficacy

    Single nucleotide polymorphisms in genes that play an important role in eliminations pathways for docetaxel (in the CYP3A4 and CYP3A5 genes) and thalidomide (CYP2C19) will be evaluated.

    Measured: Patient entry onto the study

  8. Usefulness of Dynamic Magnetic Resonance Imaging (MRI) to Monitor the Progression of Bony and Soft Tissue Disease in Metastatic Prostate Cancer

    Target lesions in the bone or soft tissues will be identified from the participant computed tomography (CT) scan. Dynamic MRI will be performed after the intravenous administration of 0.1 mmol/kg of Gadolinium chelate. Progression is defined by the RECIST criteria and is at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment starts or the appearance of new lesions.

    Measured: Baseline and at 3 month intervals until progression

  9. Changes in the Molecular Markers of Angiogenesis (Including, But Not Limited to Serum and Urine Vascular Endothelial Growth Factor (VEGF)) Before and After Administration of Docetaxel, Prednisone, Thalidomide and Bevacizumab

    Measured: Baseline and monthly

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2004 (estimated)
  2. Study start19 Apr 2005
  3. Primary completion31 Dec 2011
  4. Study completion9 Jan 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
73 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00089609
Sponsor's protocol ID
040257
Other IDs
04-C-0257
Status last verified
Mar 2018
First submitted
6 Aug 2004
Last updated
20 Apr 2018
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

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

    PubMed 7865431

  • 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.

    PubMed 1458483

  • 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.

    PubMed 7850782

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Docetaxel, Thalidomide and Prednisone in people with Prostatic Neoplasms, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Nov 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Had a Prostate-specific Antigen (PSA) Response (time frame: 21.6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00089609, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2018.

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