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

A Phase 2 Study of Itraconazole in Castrate-resistant Prostate Cancer Post-chemotherapy

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).

Study Overview

• Status: Terminated
• Conditions: Prostatic Neoplasms; Prostate Cancer; Metastatic Disease; Hormone-refractory Prostate Cancer; Castrate-resistant Prostate Cancer (CRPC); Androgen-insensitive Prostate Cancer
• Intervention / Treatment: Drug: Itraconazole

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Itraconazole; 600 mg/day oral (PO)	Drug: 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; Other Names: Sporanox; R51211

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in Serum PSA	Number of subjects with > 50% drop in serum PSA as compared to baseline, at 12 weeks and confirmed at 15 weeks	12 weeks treatment, with primary outcome assessed at 15 weeks

Collaborators and Investigators

• Sponsor: Stanford University

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): April 1, 2011
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: September 30, 2011
• First Submitted That Met QC Criteria: October 7, 2011
• First Posted (ESTIMATE): October 12, 2011

Study Record Updates

• Last Update Posted (ACTUAL): April 11, 2017
• Last Update Submitted That Met QC Criteria: March 13, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Prostatic Neoplasms; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: IRB-19413; SU-12032010-7271 (OTHER: Stanford University); PROS0037 (OTHER: OnCore)