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Prostate AdenocarcinomaPhase 2NCT01787331

Itraconazole in Treating Patients With Biochemically Relapsed Prostate Cancer

A Phase 2 study testing Itraconazole, Laboratory Biomarker Analysis and Pharmacological Study in people with Prostate Adenocarcinoma and Recurrent Prostate Carcinoma, run by University of California, San Francisco 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 studies how well itraconazole works in treating patients with biochemically relapsed prostate cancer. Itraconazole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Itraconazole, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
29 Oct 2013to 30 Sep 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

  • Histologic confirmation of adenocarcinoma of the prostate
  • Biochemically relapsed disease with a rising PSA on at least two successive 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; if the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to documents progression
  • 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
  • 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
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  • 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
  • No evidence of metastatic disease on imaging by whole body bone scan (technetium-99 or sodium fluoride [Na-F] positron emission tomography [PET] bone scan) and cross-sectional imaging of the abdomen/pelvis (computed tomography [CT] or magnetic resonance imaging [MRI]) within 6 weeks of day 1 of protocol therapy
  • Prior androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist and/or antagonist allowed for either (neo)adjuvant treatment with local therapy or for biochemical relapse
  • Last effective dose of LHRH agonist/antagonist ?expired? > 3 months prior to study entry; 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
  • 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
  • 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 ; 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
  • 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
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels less than 1.5 times ULN at study entry
  • Serum potassium greater than 3.5 mmol/L without oral supplementation
  • No history of uncontrolled hypertension (blood pressure > 160/100 mm Hg despite anti-hypertensive medication)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Estimated life expectancy greater than 5 years
  • Ability to sign written informed consent
  • Ability to swallow study drug whole as a capsule
  • Primary prostate cancer tissue available for analysis is not required for inclusion onto this study but is strongly encouraged
  • Patients who have partners of childbearing potential must be willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 1 week after last study drug administration

Who cannot join

  • 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
  • Prior bilateral orchiectomy
  • Congestive heart failure of New York Heart Association (NYHA) class III or higher severity at study entry
  • History of chronic active hepatitis
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  • Grade 2 or higher peripheral neuropathy at the time of study entry
  • 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
  • Use of systemic steroids at an equivalent dose of prednisone 5 mg/day or higher within 6 weeks of day 1 of protocol therapy
  • Use of medications or herbal supplements which are known to potentially lower serum PSA within 6 weeks of day 1 of protocol therapy
  • Use of other medications that may potentially interact with itraconazole within 1 week of study entry
  • Use of other investigational agents within 6 weeks of day 1 of protocol therapy
  • Prior pathology consistent with small cell carcinoma or prostate cancer with predominantly neuroendocrine differentiation

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California, San Francisco

    San Francisco, California, 94115

Other trials in United States

About this study

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

This phase II trial studies how well itraconazole works in treating patients with biochemically relapsed prostate cancer. Itraconazole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine whether the proportion of patients who achieve a >= 50% decline in serum prostate-specific antigen (PSA) after 12 weeks of protocol therapy with itraconazole dosed at 300 mg orally (PO) twice daily (BID) is superior to a historical control based upon the observed PSA response proportion in prior studies of non-castrating systemic therapy in men with biochemically relapsed hormone sensitive prostate cancer.

SECONDARY OBJECTIVES:

  1. To determine the median time to PSA progression from the start of protocol therapy with itraconazole among men with biochemically relapsed prostate cancer.

II. To determine the median time to clinical progression measured from the start of protocol therapy with itraconazole among men with biochemically relapsed prostate cancer.

III. To determine the median metastasis-free survival measured from the start of protocol therapy in patients treated with itraconazole for biochemically relapsed prostate cancer.

IV. To determine the mean percent change from baseline after 12 weeks of protocol therapy compared with pre-treatment in PSA doubling time.

  1. To characterize the safety profile of itraconazole in the biochemically relapsed hormone sensitive prostate cancer population, as graded by Common Toxicity Criteria (CTCAE) version 4.03. All adverse events will be tabulated by grade according to the worst grade experienced.

VI. To determine the mean steady-state itraconazole and hydroxy-itraconazole serum levels after 4 weeks of therapy with itraconazole.

Being tested
Itraconazole, Laboratory Biomarker Analysis, Pharmacological Study
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • ItraconazoleDrug

    Also called Lozanoc, Oriconazole, R 51,211, Sporanox

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT01787331
Study groupRoleWhat they receive
Treatment (itraconazole)ExperimentalPatients receive twice/day 300mg itraconazole (oral)
Receives: Drug: Itraconazole; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study

What is being measured

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

  1. Number of Patients Who Achieve a Greater Than or Equal to 50% Decline in Serum Prostate Specific Antigen (PSA)

    The number of patients with biochemically relapsed disease after prior definitive local therapy who achieve a ≥ 50% decline from baseline in serum PSA after 12 weeks of therapy with itraconazole, confirmed by repeat measurement at least 2 weeks later.

    Measured: At 12 weeks after start of treatment

Secondary outcomes (8)

  1. Mean Percent Change in PSA Doubling Time

    The mean percent change in PSA doubling time from pre-treatment to after 12 weeks of protocol therapy

    Measured: Up to 12 weeks

  2. Median Time to PSA Progression

    PSA progression defined as: 1. If no PSA decline is observed on therapy, PSA progression will be defined as an increase in serum PSA > 50% above the baseline PSA, and an absolute increase of > 2 ng/mL above baseline, confirmed by repeat measurement at least 2 weeks later. 2. If PSA declines on therapy, PSA progression will be defined as an increase in serum PSA > 50% above the nadir PSA on therapy, and an absolute increase > 2 ng/mL above the nadir, confirmed by repeat measurement at least 2 weeks later. The probability distribution of the time to PSA progression will be estimated using the Kaplan-Meier product limit method measured from the start of protocol therapy. The results will be summarized by the estimated median with 95% confidence intervals.

    Measured: Up to 2 years

  3. Median Time to Clinical Progression

    Clinical progression will be defined as the first occurrence of either the development of metastases or initiation of non-protocol therapy, and will exclude PSA-only progression.

    The probability distribution of the time to clinical progression will be estimated using the Kaplan-Meier product limit method measured from the time of start of protocol therapy. The results will be summarized by the estimated median with 95% confidence intervals.

    Measured: Up to 2 years

  4. Median Metastasis-free Survival

    The probability distribution of the time to first metastasis will be estimated using the Kaplan-Meier product limit method measured from the time of start of protocol therapy. The results will be summarized by the estimated median with 95% confidence intervals.

    Measured: Up to 2 years

  5. Percentage of Participants With Treatment-related, Adverse Changes in Vital Signs

    All patients who receive at least one dose of study drug will be analyzed for safety endpoints. All adverse events will be graded and classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4. Percentage of patients with grade 1 or higher, treatment-related adverse events based on the following vital sign assessments will be reported: blood pressure, pulse, respiration rate and temperature.

    Measured: Up to 2 years

  6. Percentage of Participants With Treatment-related, Clinical Laboratory Adverse Events

    All patients who receive at least one dose of study drug will be analyzed for safety endpoints. All adverse events will be graded and classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4.. Percentage of patients with grade 1 or higher, treatment-related adverse events based on the following labs will be reported: potassium, sodium, alkaline phosphatase, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Hematocrit, Hemoglobin, platelets, white blood cells, atypical lymphs, basophils, eosinophils, monocytes, neutrophils, blood urea nitrogen, and creatinine.

    Measured: Up to 2 years

  7. Mean Steady-state Trough Level of Serum Itraconazole

    Descriptive statistics including the mean, standard deviation, and range of steady-state trough serum levels of itraconazole and its active metabolite hydroxy-itraconazole will be determined.

    Measured: Up to 4 weeks

  8. Mean Steady-state Trough Level of Hydroxy-itraconazole

    Descriptive statistics including the mean, standard deviation, and range of steady-state trough serum levels of itraconazole and its active metabolite hydroxy-itraconazole will be determined.

    Measured: Up to 4 weeks

Timeline

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

  1. First posted8 Feb 2013 (estimated)
  2. Study start29 Oct 2013
  3. Primary completion30 May 2017
  4. Study completion30 Sep 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01787331
Sponsor's protocol ID
125513
Other IDs
NCI-2013-02375
Status last verified
Jan 2020
First submitted
6 Feb 2013
Last updated
5 Feb 2020
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Mina Lee, Haemin Hong, Won Kim, Terence W. Friedlander, Lawrence Fong, Amy M. Lin, Eric Jay Small, Mallika Sachdev Dhawan, Xiao X. Wei, Tammy J. Rodvelt, Brigid Miralda, Charles J. Ryan, and Rahul Raj Aggarwal.A phase II study of itraconazole in biochemically recurrent prostate cancer. Journal of Clinical Oncology 2018 36:6_suppl, 362-362

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Itraconazole, Laboratory Biomarker Analysis and Pharmacological Study in people with Prostate Adenocarcinoma and Recurrent Prostate Carcinoma, run by University of California, San Francisco 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 32 inclusion and 13 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 5 Feb 2020. 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 23 Oct 2018). 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 Patients Who Achieve a Greater Than or Equal to 50% Decline in Serum Prostate Specific Antigen (PSA) (time frame: At 12 weeks after start of 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 NCT01787331, which also lists 1 linked publication.

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 5 Feb 2020.

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