Skip to main content

Summary

Eligibility
for males ages 18 years and up
Location
at San Francisco, California
Dates
study started
estimated completion:
Principal Investigator

Description

Summary

This study is being done to test an investigational drug called itraconazole in the treatment of prostate cancer.

Official Title

Hedgehog Inhibition as a Non-Castrating Approach to Hormone Sensitive Prostate Cancer: A Phase II Study of Itraconazole in Biochemical Relapse

Details

This is a phase II, single arm study of itraconazole dosed at 300 mg PO BID in patients with noncastrate, non-metastatic, biochemically relapsed prostate cancer after prior definitive local therapy. Simon's two stage minimax design will be followed for accrual and include an interim test for lack of efficacy. There is a pre-specified stopping rule for safety after 10 patients have been treated for a minimum of 8 weeks of protocol therapy.

Keywords

Prostate Cancer biochemically relapsed hormone sensitive non-metastatic after prior definitive local therapy PSA Hedgehog-signaling pathway Itraconazole Hydroxyitraconazole

Eligibility

You can join if…

Open to males ages 18 years and up

  1. Histologic confirmation of adenocarcinoma of the prostate
  2. Biochemically relapsed disease with a rising PSA on at least two consecutive measurements at least two weeks apart after prior definitive local therapy (radical prostatectomy, external beam radiation, or brachytherapy) or combination of radical prostatectomy and radiotherapy (RT) with curative intent
  3. Prior primary or salvage radiation or not a candidate for salvage radiation due to patient preference or clinical assessment based upon disease characteristics and/or patient co-morbidities.
  4. Minimum PSA: If no prior androgen deprivation therapy (ADT) for biochemical relapse:

    • 1.0 ng/mL if prior radical prostatectomy with or without adjuvant/salvage radiation therapy, confirmed by repeat measurement at least 2 weeks later, or
    • Nadir + 2 ng/mL if prior RT alone without prior radical prostatectomy, confirmed by repeat measurement at least 2 weeks later If prior ADT for biochemical relapse:
    • 4.0 ng/mL or> 2 ng/mL above nadir on prior cycle of ADT, whichever is higher,confirmed by repeat measurement at least 2 weeks later
  5. No evidence of metastatic disease on imaging by whole body bone scan (technetium-99 or Na-F PET bone scan) and cross-sectional imaging of the abdomen/pelvis (CT or MRI)within 6 weeks of Day 1 of protocol therapy
  6. Prior androgen deprivation therapy (ADT) with LHRH agonist and/or antagonist allowed for either (neo)adjuvant treatment with local therapy or for biochemical relapse
  7. Last effective dose of LHRH agonist/antagonist "expired"> 3 months prior to study entry.
  8. For example, a patient receiving LHRH agonist injection every 3 months would be eligible provided their last injection was> 6 months prior to Day 1 of protocol therapy. A patient receiving LHRH agonist injections every 4 months will be eligible provided last injection was> 7 months prior to Day 1 of protocol therapy.
  9. Serum testosterone level: If no prior androgen deprivation therapy:

    • A single measurement greater than 150 ng/dL within 3 months of day 1 of protocol therapy If prior androgen deprivation therapy (either in adjuvant or biochemical relapse setting):

    The two most recent measurements of serum testosterone prior to Day 1 of protocol therapy must fulfill the following criteria:

    • Both measurements are greater than 150 ng/dL.
    • The two measurements are spaced at least 14 days apart.
    • Both must be measured within 3 months of Day 1 of protocol therapy.
    • There must not be an increase of> 50 ng/dL between these two successive measurements.
  10. PSA doubling time (PSADT) ≤ 15 months, calculated based upon all serum PSA measurements obtained within 3 months prior to Day 1 of protocol therapy, with a minimum of three PSA measurements spaced at least 14 days apart (see section 6). PSA values obtained when serum testosterone was known to be less than 150 ng/dL, prior to local therapy, or within three months of last dose of LHRH agonist/antagonist or antiandrogen will be excluded from the calculation of the PSADT. PSADT calculation to be carried out using the following website:http://nomograms.mskcc.org/Prostate/PsaDoublingTime.aspx
  11. Total bilirubin less than 1.5 times upper limit of normal (ULN), or less than 3 times ULN at study entry in a patient with documented Gilbert‟s disease.
  12. ALT and AST levels less than 1.5 times ULN at study entry
  13. Serum potassium greater than 3.5 mmol/L without oral supplementation
  14. No history of uncontrolled hypertension (blood pressure> 160/100 mm Hg despite anti-hypertensive medication)
  15. ECOG performance status of 0 or 1
  16. Estimated life expectancy greater than 5 years
  17. Age greater than or equal to 18 years at time of study entry
  18. Ability to sign written informed consent
  19. Ability to swallow study drug whole as a capsule
  20. Primary prostate cancer tissue available for analysis is not required for inclusion onto this study but is strongly encouraged.

You CAN'T join if...

  1. Castrate-resistant disease, as evidenced by either:

    • Rising PSA on 2 consecutive measurements at least 2 weeks apart with concurrent documented serum testosterone < 50 ng/dL at the time of PSA measurement, or
    • Rising PSA on 2 consecutive measurements at least 2 weeks apart measured within 3 months after last LHRH agonist/antagonist injection
  2. Prior bilateral orchiectomy
  3. Congestive heart failure of NYHA class III or higher severity at study entry
  4. History of chronic active hepatitis
  5. Grade 2 or higher peripheral neuropathy at the time of study entry
  6. Use of 5-alpha reductase antagonist (i.e. finasteride, dutasteride) or antiandrogen(i.e. flutamide, bicalutamide) within 6 weeks of Day 1 of protocol therapy
  7. Use of systemic steroids at an equivalent dose of prednisone 5 mg/day or higher within 6 weeks of Day 1 of protocol therapy
  8. Use of medications or herbal supplements which are known to potentially lower serum PSA within 6 weeks of Day 1 of protocol therapy
  9. Use of other medications that may potentially interact with itraconazole within 1 week of study entry
  10. Use of other investigational agents within 6 weeks of Day 1 of protocol therapy
  11. Prior pathology consistent with small cell carcinoma or prostate cancer with predominantly neuroendocrine differentiation

Location

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT01787331
Phase
Phase 2
Lead Scientist
Rahul Aggarwal
Study Type
Interventional
Last Updated
June 1, 2017