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Adenocarcinoma of the ProstatePhase 3NCT00110214

Docetaxel and Prednisone With or Without Bevacizumab in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

A Phase 3 study testing docetaxel, prednisone and bevacizumab in people with Adenocarcinoma of the Prostate and Hormone-resistant Prostate Cancer, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

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

Official record
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Trial summary

This randomized phase III trial is studying docetaxel, prednisone, and bevacizumab to see how well they work compared to docetaxel and prednisone in treating patients with prostate cancer that did not respond to hormone therapy. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
docetaxel, prednisone and bevacizumab
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,050 participants
Where
2 sitesUnited States
Study dates
Apr 2005to Aug 2011
Phase
Phase 3
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

  • Patients must have histologically documented adenocarcinoma of the prostate with progressive systemic (clinically metastatic disease documented on bone, CT or MRI scan) disease despite castrate levels of testosterone due to orchiectomy or LHRH agonist; castrate levels of testosterone must be maintained
  • All eligible patients must have a Gleason sum based on biopsy or TURP at the time of registration
  • At the time of enrollment, patients must have evidence of progressive metastatic disease, either:
  • Measurable disease with any level of serum PSA OR
  • Non-measurable disease with PSA ≥ 5 ng/ml; patients with PSA ≥ 5 ng/ml only and no other radiographic evidence of metastatic prostate cancer are not eligible
  • Definition of Measurable Disease/Target Lesions:
Show all 54Show fewer
  • Any lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques: 1) physical exam for clinically palpable lymph nodes and superficial skin lesions, 2) chest X-ray for clearly defined lung lesions surrounded by aerated lung OR those lesions measured as ≥ 10 mm with a spiral CT or MRI scan
  • Measurable lesions (up to a maximum of 10 in number) representative of all organs involved to be identified as target lesions; the sum of the longest diameters (LD) for all target lesions will be calculated and reported as baseline sum LD
  • If measurable disease is confined to a solitary lesion and is not consistent with prostate cancer, then its neoplastic nature must be confirmed by histology
  • Ultrasound may not be used to measure tumor lesions that are not easily accessible clinically
  • Definition of Non-measurable Disease/Non-target Lesions:
  • Non-target lesions include all other lesions not included in above, including small lesions with longest diameter < 20 mm with conventional techniques or < 10 mm with spiral CT scan and truly non-measurable lesions, which include:
  • Bone lesions
  • Pleural or pericardial effusions, ascites
  • CNS lesions, leptomeningeal disease
  • Irradiated lesions, unless progression documented after RT
  • Patients must have demonstrated evidence of progressive disease since the most recent change in therapy; progressive disease is defined as any one of the following (measurable disease, bone scan, or PSA progression):
  • Measurable Disease Progression: Objective evidence of increase > 20% in the sum of the longest diameters (LD) of target lesions from the time of maximal regression or the appearance of one or more new lesions
  • Bone Scan Progression: Appearance of one or more new lesions on bone scan attributable to prostate cancer along with a PSA ≥ 5 ng/ml will constitute progression
  • PSA Progression: An elevated PSA (≥ 5 ng/mL) which has risen serially on at least two occasions after the discontinuation of antiandrogen therapy, each at least one week apart; if the confirmatory PSA (#3) value is less than screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression
  • The reference PSA value (#1) must be measured at the time of the discontinuation of antiandrogen therapy; and at least 2 PSA measurements must be made following the end of antiandrogen therapy and prior to registration
  • (For the purposes of the nomogram calculator, the last PSA value recorded prior to the initiation of treatment will be considered the baseline PSA)
  • Progression despite standard androgen deprivation therapy (i.e., LHRH agonist and/or orchiectomy)
  • All antiandrogens (e.g., flutamide, megestrol acetate [even if taken for hot flashes], bicalutamide and nilutamide) of any dose must be discontinued at least 4 weeks prior to registration; if improvement following antiandrogen withdrawal is noted, progression must be established using the criteria above
  • Primary testicular androgen suppression (e.g., with an LHRH agonist) should not be discontinued
  • At least 4 weeks since any other hormonal therapy, including ketoconazole and aminoglutethimide; the only exception to this time frame is that 5α-reductase inhibitors (e.g., finasteride, dutasteride) may be discontinued any time prior to registration
  • No prior cytotoxic chemotherapy, including estramustine or suramin
  • No prior anti-angiogenesis agents, including thalidomide and bevacizumab
  • ≥ 4 weeks since major surgery and fully recovered
  • ≥ 4 weeks since any prior radiation (including palliative) and fully recovered
  • ≥ 8 weeks since the last dose of Strontium-89 or Samarium
  • Patients receiving a bisphosphonate must be on a stable dose and must have started the bisphosphonate ≥ 4 weeks prior to initiating protocol treatment. Patients do not have to be on a bisphosphonate to qualify for the study; patients may initiate bisphosphonate therapy after completion of Cycle 1, if clinically indicated
  • Patients enrolled on CALGB 90202 who have documented disease progression and have received at least 4 weeks of open label zoledronic acid treatment, are eligible for this study.
  • No known brain metastases (brain imaging (MRI/CT) is not required)
  • No current congestive heart failure (New York Heart Association Class II, III or IV)
  • Patients with history of hypertension must be well controlled (< 160/90) on a regimen of anti-hypertensive therapy
  • Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an in-range INR (usually between 2 and 3) or be on a stable dose of LMW heparin; patients receiving anti-platelet agents are also eligible; in addition, patients who are on daily prophylactic aspirin or anticoagulation for atrial fibrillation are eligible
  • No significant history of bleeding events or GI perforation
  • Patients with a history of significant bleeding episodes (e.g., hemoptysis, upper or lower GI bleeding) within 6 months of registration are not eligible
  • Patients with a history of GI perforation within 12 months of registration are not eligible.
  • No recent (within 12 months) arterial thrombotic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina or angina requiring surgical or medical intervention in the past 12 months, or myocardial infarction (MI); patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) or any other arterial thrombotic event are also ineligible
  • No serious or non-healing wound, ulcer or bone fracture
  • No peripheral neuropathy ≥ grade 2
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies are not eligible
  • PC-Spes, Saw Palmetto, and St. John's Wort must be discontinued before registration; the discontinuation of other herbal medications and food supplements is strongly encouraged; patients may continue on daily vitamins and calcium supplements
  • ECOG performance status: 0-2
  • ANC ≥ 1500/μL
  • Platelet count ≥ 100,000/μL
  • Creatinine ≤ 1.5 x upper limits of normal
  • Bilirubin ≤ 1.5 x upper limits of normal
  • For patients with Gilbert's Disease, ≤ 2.5 X ULN is allowed
  • AST ≤ 1.5 x upper limits of normal
  • PSA ≥ 5 ng/mL (if non-measurable disease)
  • Urine protein to creatinine ratio < 1.0

Who cannot join

None listed.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Cancer and Leukemia Group B

    Chicago, Illinois, 60606

  • Yale University

    New Haven, Connecticut, 06520

Other trials in United States

About this study

Official title: A Randomized Double-Blinded Placebo Controlled Phase III Trial Comparing Doctaxel and Prednisone With and Without Bevacizumab (IND #7921, NSC #704865) in Men With Hormone Refractory Prostate Cancer

This randomized phase III trial is studying docetaxel, prednisone, and bevacizumab to see how well they work compared to docetaxel and prednisone in treating patients with prostate cancer that did not respond to hormone therapy. Drugs used in chemotherapy, such as docetaxel and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether docetaxel, prednisone, and bevacizumab are more effective than docetaxel and prednisone in treating prostate cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine if the addition of bevacizumab to docetaxel and prednisone increases overall survival compared to docetaxel and prednisone alone in patients with HRPC.

SECONDARY OBJECTIVES:

  1. To compare the progression-free survival of these two regimens in patients with HRPC.

II. To compare the two regimens on the proportion of patients who experience a 50% post-therapy PSA decline from baseline.

III. To compare the two regimens with respect to the proportion of patients who experience grade 3 or higher toxicities.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to predicted 24-month survival probability (< 10% vs 10-29.9% vs ≥ 30%), age (< 65 years vs ≥ 65 years), and prior history of arterial events (i.e., cardiac ischemia/infarction, CNS cerebrovascular ischemia, peripheral arterial ischemia, or CNS hemorrhage) (yes vs no). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive docetaxel IV over 1 hour and placebo IV over 30-90 minutes on day 1. Patients also receive oral prednisone once daily on days 1-21.

ARM II: Patients receive docetaxel and prednisone as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1.

In both arms, courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 5 years.

Being tested
docetaxel, placebo, prednisone, bevacizumab, laboratory biomarker analysis
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • docetaxelDrug

    Also called RP 56976, Taxotere, TXT

    Given IV

  • placeboOther

    Also called PLCB

    Given IV

  • prednisoneDrug

    Also called DeCortin, Deltra

    Given orally

  • bevacizumabBiological

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00110214
Study groupRoleWhat they receive
Arm IExperimentalPatients receive docetaxel IV over 1 hour and placebo IV over 30-90 minutes on day 1. Patients also receive oral prednisone once daily on days 1-21.
Receives: Drug: docetaxel; Other: placebo; Drug: prednisone; Other: laboratory biomarker analysis
Arm IIExperimentalPatients receive docetaxel and prednisone as in arm I. Patients also receive bevacizumab IV over 30-90 minutes on day 1.
Receives: Drug: docetaxel; Drug: prednisone; Biological: bevacizumab; Other: laboratory biomarker analysis

What is being measured

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

  1. Overall Survival

    Overall Survival (OS) was measured from the date of randomization to date of death due to any cause. OS was estimated using the Kaplan Meier method.

    Measured: Duration of study (up to 5 years)

Secondary outcomes (3)

  1. Proportion of Participants Who Experienced at Least a 50% Post-therapy PSA (Prostate-Specific Antigen) Decline

    PSA decline will be reported on all patients and will be defined as a decrease in PSA value by >= 50% for two successive evaluations at least 4 weeks apart. The reference PSA value for these declines should be measured within 2 weeks before starting therapy.

    Measured: Duration of study (up to 5 years)

  2. Progression-free Survival (PFS)

    PFS was defined as the data of randomization to date of progression or death due to any cause, whichever occurs first. PFS was estimated using the Kaplan Meier method.

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

    Measured: Duration of study (up to 5 years)

  3. Proportion of Participants Who Experience (Maximum) Grade 3 or Higher Toxicities

    The National Cancer Institute (NCI) Criteria for Adverse Events(CTCAE) Version 3.0 was used to evaluate toxicity. These events were considered at least possibly related to treatment.

    Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death

    Measured: During treatment (up to 2 years)

Timeline

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

  1. First posted5 May 2005 (estimated)
  2. Study startApr 2005
  3. Primary completionMar 2010
  4. Study completionAug 2011

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
1,050 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00110214
Sponsor's protocol ID
NCI-2012-02814
Other IDs
NCI-2012-02814, CDR0000427290, CALGB-90401, CALGB-90401, P30CA014236, U10CA031946
Status last verified
Dec 2012
First submitted
4 May 2005
Last updated
9 May 2014

Publications

  • Quintanilha JCF, Kelly WK, Innocenti F. Contribution of plasma levels of VEGF-A and angiopoietin-2 in addition to a genetic variant in KCNAB1 to predict the risk of bevacizumab-induced hypertension. Pharmacogenomics J. 2024 Jul 12;24(4):22. doi: 10.1038/s41397-024-00342-1.

    PubMed 38992025

  • Quintanilha JCF, Wang J, Sibley AB, Jiang C, Etheridge AS, Shen F, Jiang G, Mulkey F, Patel JN, Hertz DL, Dees EC, McLeod HL, Bertagnolli M, Rugo H, Kindler HL, Kelly WK, Ratain MJ, Kroetz DL, Owzar K, Schneider BP, Lin D, Innocenti F. Bevacizumab-induced hypertension and proteinuria: a genome-wide study of more than 1000 patients. Br J Cancer. 2022 Feb;126(2):265-274. doi: 10.1038/s41416-021-01557-w. Epub 2021 Oct 6.

    PubMed 34616010

  • Quintanilha JCF, Liu Y, Etheridge AS, Yazdani A, Kindler HL, Kelly WK, Nixon AB, Innocenti F. Plasma levels of angiopoietin-2, VEGF-A, and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance). Angiogenesis. 2022 Feb;25(1):47-55. doi: 10.1007/s10456-021-09799-1. Epub 2021 May 24.

    PubMed 34028627

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing docetaxel, prednisone and bevacizumab in people with Adenocarcinoma of the Prostate and Hormone-resistant Prostate Cancer, run by National Cancer Institute (NCI) at 2 sites 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 54 inclusion and 0 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 9 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 17 Apr 2013). 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?

Overall Survival (time frame: Duration of study (up to 5 years)). 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 NCT00110214, 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 9 May 2014.

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