Study of Itraconazole in Castrate-resistant Prostate Cancer (CRPC) Post-chemotherapy

NCT ID: NCT01450683

Last Updated: 2017-04-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2011-04-30

Brief Summary

This study evaluates if itraconazole causes a reduction in the serum levels of prostate-specific antigen (PSA) in male subjects with castration-resistant prostate cancer (CRPC).

Detailed Description

Castration-resistant prostate cancer (CRPC) is also known as "androgen-insensitive" or "hormone-refractory" prostate cancer. While numerous therapies impact biochemical response in the setting of CRPC, there remains unmet medical need, largely expressed as the lack of durable response. New therapies that extend survival of patients beyond that provided by chemotherapy are needed.

It is hypothesized that the triazole antifungal drug itraconazole, through its activity as a potent inhibitor of the Hedgehog (Hh) signaling pathway via the Smoothened (Smo) pathway, may provide clinical benefit in the treatment of prostate cancer. The Hh signaling pathway is a critical embryonic developmental pathway whose aberrant activity has been implicated in the growth and metastases of a variety of tumor types including prostate cancer. Itraconazole is structurally related to ketoconazole, demonstrated to reduce serum PSA by more than 50% in about 20 to 25% of treated prostate cancer subjects.

This study will assess efficacy on the basis of serum levels of PSA, an established surrogate endpoint for efficacy in prostate cancer.

Conditions

Prostate Cancer; Prostatic Neoplasms; Castrate-resistant Prostate Cancer (CRPC); Androgen-insensitive Prostate Cancer; Hormone-refractory Prostate Cancer; Metastatic Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Itraconazole

600 mg/day oral (PO)

Group Type: EXPERIMENTAL

Itraconazole

Intervention Type: DRUG

600 mg/day oral (PO)

IUPAC name: (2R,4S)-rel-1-(Butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one

Interventions

Itraconazole

600 mg/day oral (PO)

IUPAC name: (2R,4S)-rel-1-(Butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one

Intervention Type: DRUG

Other Intervention Names

Sporanox; R51211

Eligibility Criteria

Inclusion Criteria

• Male aged ≥ 18 years
• Life expectancy ≥ 6 months
• Histologically- or cytologically-confirmed adenocarcinoma of the prostate
• Metastatic disease or prior history of metastases, as documented by positive bone scan or metastatic lesions on CT or MRI
• Prostate cancer progression, as documented by PSA according to PCWG2 or radiographic progression according to RECIST criteria version 1.1
• Progression must have been during or after docetaxel based chemotherapy.
• Surgically or medically castrated, with testosterone levels of < 50 ng/dL (< 2.0 nM). If the patient is currently being treated with LHRH agonists (patient who have not undergone an orchiectomy), this therapy must have been initiated at least 4 weeks prior to Cycle 1 Day 1 and treatment must be continued throughout the study.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• Hemoglobin ≥ 10.0 g/dL
• Platelet count ≥100,000 microliters
• Serum creatinine ≤ 2, OR a calculated creatinine clearance ≥ 40 mL/min
• Serum bilirubin < 1.5 x ULN (except for patients Gilbert's disease)
• AST or ALT < 2.5 x ULN
• Able to swallow the study drug whole as a tablet
• Willing and able to provide written informed consent

Exclusion Criteria

• Known brain metastasis
• Radiation therapy within 4 weeks of Cycle 1, Day 1
• Prior systemic treatment with an azole drug (eg, fluconazole, ketoconazole) within 4 weeks of Cycle 1, Day 1
• Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1 (patients whose PSA did not decline for ≥ 3 months months in response to antiandrogen given as a 2nd line or later intervention will require only a 2-week washout prior to Cycle 1,Day 1)
• Prior Bicalutamide (Casodex), nilutamide (Nilandron) treatment within 6 weeks of Cycle 1 Day 1 (patients whose PSA did not decline for ≥ 3 months in response to antiandrogen given as a 2nd line or later intervention will require only a 2-week washout prior to Cycle 1 Day 1)
• Known active or symptomatic viral hepatitis or chronic liver disease
• Clinically significant heart disease as evidenced by myocardial infarction or arterial thrombotic events in the past 6 months; severe or unstable angina
• Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months
• Administration of an investigational therapeutic within 30 days of Cycle 1, Day 1
• Any condition which, in the opinion of the investigator, would preclude the patient's participation in this trial.
• No more than 3 prior chemotherapy regimens.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Sandy Srinivas

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dr. Sandy Srinivas

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

Other Identifiers

SU-12032010-7271

Identifier Type: OTHER

Identifier Source: secondary_id

PROS0037

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-19413

Identifier Type: -

Identifier Source: org_study_id