A Phase II Study of Itraconazole in Biochemical Relapse

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Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and overOtherCC#125513

Trial Description


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

Further Study Information

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.

Eligibility Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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

Trial Contact Information

Trial Lead Organizations/Sponsors

UCSF Helen Diller Family Comprehensive Cancer Center

    Rahul Aggarwal, MD, Principal Investigator
    Paula Dutton, BS
    Ph: 415-885-7871
    Email: walshp@medicine.ucsf.edu

    Trial Sites


    San Francisco

    UCSF Helen Diller Family Comprehensive Cancer Center

    Paula Dutton
    Ph: 415-885-7871
    Email: mailto:walshp@medicine.ucsf.edu

    Rahul Aggarwal, MD
    Ph: 415-353-9278
    Email: rahul.aggarwal@ucsf.edu

    Rahul Aggarwal, MD
    Principal Investigator

    Link to the current ClinicalTrials.gov record.
    NLM Identifier NCT01787331
    ClinicalTrials.gov processed this data on October 20, 2014

    Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.