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Adenocarcinoma of the ProstatePhase 2NCT00466752

Sorafenib Tosylate and Gene Expression Analysis in Patients Undergoing Surgery For High-Risk Localized Prostate Cancer

A Phase 2 study testing sorafenib tosylate, microarray analysis and immunohistochemistry staining method in people with Adenocarcinoma of the Prostate and Stage II Prostate Cancer, run by University of Washington 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
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Trial summary

This phase II trial is studying sorafenib tosylate and gene expression in patients undergoing surgery for high-risk localized prostate cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
sorafenib tosylate, microarray analysis and immunohistochemistry staining method
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
Dec 2006to 1 Jul 2011
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

  • Histologically confirmed adenocarcinoma of the prostate
  • Radical prostatectomy and lymph node dissection planned as primary therapy in a patient with acceptable surgical risk (e.g., cardiovascular, pulmonary, and functional status)
  • 10 year or longer life expectancy
  • Any of the following high-risk features: Clinical stage T2b (palpable bilateral involvement) OR surgically resectable T3 OR PSA >= 20 ng/ml OR overall Gleason grade >= 8
  • No evidence of bone metastases on bone scan
  • No evidence of lymph nodes >= 2 cm in diameter on pelvic CT scan
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  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Hemoglobin >= 9.0 g/dl
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Total bilirubin =< 1.5 x ULN
  • ALT =< 2.5 x the ULN
  • AST =< 2.5 x the ULN
  • INR =< 1.5 and aPTT within normal limits
  • Creatinine =< 1.5 x ULN or creatinine clearance > 60mL/min/1.73 m^2
  • Men must agree to use adequate contraception (abstinence, hormonal in female partner, or barrier method of birth control) prior to study entry, for the duration of study participation, and for at least two weeks after stopping treatment
  • Signed informed patient consent

Who cannot join

  • Prior therapy for prostate cancer including conventional androgen deprivation therapy, radiotherapy (external beam or brachytherapy), cryotherapy, and/or cytotoxic chemotherapy
  • Any known metastasis; patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis
  • Significant active medical illness which in the opinion of the investigator would preclude protocol treatment
  • Another malignancy, other than non-melanoma skin cancer, during the past 5 years
  • History of bleeding diathesis or unexpected surgical bleeding
  • Patients with active coagulopathy
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  • Cardiac disease: Congestive heart failure > class II NYHA; patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
  • Uncontrolled hypertension, as defined by systolic blood pressure consistently in excess of 150 mmHg, or diastolic pressure consistently in excess of 90 mmHg
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
  • Pulmonary hemorrhage/bleeding event >= CTCAE Grade 2 within 4 weeks of first dose of study drug
  • Any other hemorrhage/bleeding event >= CTCAE Grade 3 within 4 weeks of first dose of study drug
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
  • Patients may not be concurrently receiving any chemotherapy, immunotherapy, hormonal therapy, or molecular targeted agents to treat their prostate cancer
  • Patients may not be receiving any other investigational agents
  • Therapeutic anticoagulation with heparin, low-molecular weight heparin, or warfarin within the last 4 weeks
  • Patients may not be using rifampin, digoxin, quinidine, ketoconazole, itraconazole, cyclosporine, carbamazepine, phenytoin, phenobarbital, St. John's Wart, or products containing grapefruit juice
  • Patients may not be using bevacizumab or any other drugs that target VEGF or VEGF receptors
  • Active clinically significant infections (>= grade 2 NCI-CTCAE version 3.0); patients may enroll after infection resolves
  • HIV-positive patients receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with Sorafenib
  • Any condition that impairs patient's ability to swallow whole pills
  • Any malabsorption problem

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase II Study of Sorafenib (Nexavar®) Prior to Radical Prostatectomy in Patients With High-Risk Localized Prostate Cancer

This phase II trial is studying sorafenib tosylate and gene expression in patients undergoing surgery for high-risk localized prostate cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Studying samples of blood and tumor tissues in the laboratory from patients with prostate cancer may help doctors learn more about changes that occur in DNA after treatment with sorafenib tosylate

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the gene expression changes (transcript profiles) between pre- and post-treatment tumor specimens in order to determine the molecular impact of multi-kinase inhibition on prostate cancer. While this analysis will initially be targeted to tumor cells, gene expression changes in the surrounding stromal tissue may also be analyzed.

SECONDARY OBJECTIVES:

  1. To determine if specific downstream protein effectors (i.e. ERK, AKT, and S6- kinase) of Sorafenib kinase targets are affected by changes in protein phosphorylation by immunohistochemistry.

II. To provide evidence that Sorafenib has significant anti-tumor effect by comparison of pre- and post-treatment immunohistochemical markers of apoptosis (caspase-3), cell proliferation (Ki-67), and angiogenesis (microvessel density).

III. To determine the pathologic complete response rate, defined as absence of cancer in the prostatectomy specimen.

IV. To determine rates of positive surgical margins, extracapsular extension, seminal vesicle and lymph node involvement with tumor in comparison with Memorial Sloan Kettering pre-operative nomogram predictions.

  1. To determine the percentage of patients with a >= 25% and >= 50% decline in PSA while receiving Sorafenib.

VI. To determine tissue Sorafenib levels in prostate tumors after treatment and correlate with molecular, clinical, and/or pathologic outcomes.

VII. To describe changes in overall histology after treatment with Sorafenib and correlate with molecular and clinical outcomes.

VIII. To determine if patients with baseline alterations in phospho-ERK, phospho-AKT, and phospho-S6-kinase expression correlate with treatment related molecular, clinical, and/or pathologic outcomes.

IX. To collect tissue samples for future analysis of correlative biomarkers of prognosis or treatment response.

  1. To collect frozen plasma for future analysis of correlative biomarkers of treatment response (no genetic analysis will be performed on these specimens).

OUTLINE:

Patients receive sorafenib tosylate orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 or 2 days after completion of sorafenib tosylate, patients undergo radical prostatectomy on approximately day 43.

After completion of study treatment, patients are followed up for 6-10 weeks.

Being tested
sorafenib tosylate, microarray analysis, immunohistochemistry staining method, gene expression analysis, needle biopsy
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • sorafenib tosylateDrug

    Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar

    Given PO

  • microarray analysisGenetic

    Also called gene expression profiling

    Correlative studies

  • immunohistochemistry staining methodOther

    Also called immunohistochemistry

    Correlative studies

  • gene expression analysisGenetic

    Correlative studies

  • needle biopsyProcedure or surgery

    Also called aspiration biopsy, puncture biopsy

    Correlative studies

  • therapeutic conventional surgeryProcedure or surgery

    Undergo prostatectomy

  • laboratory biomarker analysisOther

    Correlative studies

  • western blottingGenetic

    Also called Blotting, Western, Western Blot

    Correlative studies

  • RNA analysisGenetic

    Correlative studies

Study groups in NCT00466752
Study groupRoleWhat they receive
Treatment (enzyme inhibitor) 48hr stopExperimentalPatients receive sorafenib tosylate PO BID on days 1-14. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 2 days after completion of sorafenib tosylate, patients undergo radical prostatectomy on approximately day 43.
Receives: Drug: sorafenib tosylate; Genetic: microarray analysis; Other: immunohistochemistry staining method; Genetic: gene expression analysis; Procedure: needle biopsy; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Genetic: western blotting; Genetic: RNA analysis
Treatment (enzyme inhibitor) 24hr stopExperimentaltients receive sorafenib tosylate PO BID on days 1-14. Treatment repeats every 2 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 1 day after completion of sorafenib tosylate, patients undergo radical prostatectomy on approximately day 43.
Receives: Drug: sorafenib tosylate; Genetic: microarray analysis; Other: immunohistochemistry staining method; Genetic: gene expression analysis; Procedure: needle biopsy; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis; Genetic: western blotting; Genetic: RNA analysis

What is being measured

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

  1. Efficacy as Assessed by Number of Patients With Changes Across Transcript Profiles by Microarray Analysis in Prostate Cancer Specimens, Specifically Those With Complete Pathologic Response.

    Determined by changes across transcript profiles, by microarray analysis, in pre- versus post-treatment prostate cancer specimens (minimum 50 day time frame between these). Proportion of patients with complete pathologic response.

    Measured: Pre- versus post-treatment

Secondary outcomes (2)

  1. Number of Participants With Complete Pathologic Response

    Proportion of Patients with at least 50% decline in PSA on Day 1 of Cycle 2, Day 1 of Cycle 3, and on day of radical prostatectomy.

    Measured: Day 1 of cycles 2 and 3, and day of radical prostatectomy. Each cycle is 2 weeks.

  2. Number of Participants With at Least 25% Reduction in PSA

    Proportion of Patients with at least 25% decline in PSA on Day 1 of Cycle 2, Day 1 of Cycle 3, and on day of radical prostatectomy.

    Measured: Day 1 of cycles 2 and 3 and on the day of radical prostatectomy. Each cycle is 2 weeks.

Timeline

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

  1. First posted27 Apr 2007 (estimated)
  2. Study startDec 2006
  3. Primary completionApr 2010
  4. Study completion1 Jul 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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00466752
Sponsor's protocol ID
6307
Other IDs
NCI-2010-00604
Status last verified
Nov 2017
First submitted
25 Apr 2007
Last updated
22 Nov 2017
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing sorafenib tosylate, microarray analysis and immunohistochemistry staining method in people with Adenocarcinoma of the Prostate and Stage II Prostate Cancer, run by University of Washington 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 17 inclusion and 22 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 22 Nov 2017. 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 22 Nov 2017). 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?

Efficacy as Assessed by Number of Patients With Changes Across Transcript Profiles by Microarray Analysis in Prostate Cancer Specimens, Specifically Those With Complete Pathologic Response. (time frame: Pre- versus post-treatment). 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 NCT00466752.

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 22 Nov 2017.

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