Phase I/II Study of Hydroxychloroquine With Itraconazole With Biochemically Recurrent Prostate Cancer

NCT03513211 | Completed Phase 1 DMC

• 1 other identifier: HITMAN
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Recent pre-clinical work has suggested that Itraconazole has an anti-cancer effect that works synergistically with hydroxychloroquine. This may delay the need for androgen deprivation therapy (ADT) and its associated toxicities in men with biochemically recurrent (BCR) prostate cancer. This study aims to determine feasibility, safety and efficacy of suba-itraconazole (SI) in combination with hydroxychloroquine (HQ) in the treatment of biochemically recurrent (BCR) prostate cancer as means of delaying time to commencement of androgen deprivation therapy.

Conditions

Prostate Cancer

Keywords

Biochemically recurrent prostate cancer; Hormone sensitive prostate cancer

Outcome Measures

Primary Outcomes (1)

• Determination of Recommended Phase II Dose of Hydroxychloroquine in combination with Suba-itraconazole

  Recommended Phase II Dose

  6 months

Secondary Outcomes (4)

• PSA response rate

  1 year

• Composite safety

  1 year

• Time to ADT commencement

  1 year

• Metastasis-free survival

  1 year

Study Arms (2)

Dose escalation arm

EXPERIMENTAL

Suba-itraconazole in combination dose escalating hydroxychloroquine H

Drug: SUBA-itraconazole; Drug: Hydroxychloroquine

Phase II: Dose expansion arm

EXPERIMENTAL

Suba-itraconazole with recommended phase II dose of hydroxychloroquine as determined by phase I arm.

Drug: SUBA-itraconazole; Drug: Hydroxychloroquine

Interventions

SUBA-itraconazole DRUG

150mg PO BD

Dose escalation arm; Phase II: Dose expansion arm

Hydroxychloroquine DRUG

Escalating doses in Rolling 6 Phase I

Dose escalation arm; Phase II: Dose expansion arm

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males ≥ 18 years of age with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
• Prostate cancer initially treated by radical prostatectomy, radiotherapy (including brachytherapy) or both, with curative intent
• PSA ≥ 1 ng/ml with at least two sequential rises at least 1 week apart according to PCWG3.
• Serum testosterone ≥ 5 nmol/L
• QTc ≤ 470 msec using Fridericia correction formula
• Adequate bone marrow function with platelets ≥ 100 x 10\^9/L, ANC ≥ 1.5 x 10\^9/L, Hb ≥ 100 g/L in the absence of transfusion
• Adequate liver function with ALT/AST \< 1.5 x ULN, bilirubin \< 1.5 x ULN
• Adequate renal function with creatinine clearance \> 50 ml/min
• ECOG Performance Status ≤ 1
• Able to start study treatment within 28 days of consent
• Willing and able to comply with all study requirements, including treatment (e.g. able to swallow tablets), timing and/or nature of required assessments
• Signed, written informed consent

You may not qualify if:

• Contraindications to investigational product including hypersensitivity, treatment with any CYP3A4 inducer or inhibitor or known G6PD deficiency. If on a statin, must be changed to rosuvastatin or ceased, as appropriate
• Evidence of metastatic disease on conventional WBBS or CT. However low volume regional nodes (≤ N1, up to the aortic bifurcation) may be accepted in asymptomatic patients.
• PSA doubling time ≤ 3 months calculated using MSKCC calculator (https://www.mskcc.org/nomograms//prostate/psa-doubling-time)
• Prior systemic therapy for advanced cancer prostate cancer such as hormonal therapy or chemotherapy; neo/adjuvant hormonal therapy allowed if ≤ 24 months total duration and ceased ≥ 12 months prior to enrolment
• Life expectancy of ≤ 1 year
• History of another invasive cancer within 3 years before screening with the exception of fully treated cancer with remote probability of recurrence
• Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
• Use of hydroxychloroquine and/or itraconazole for any indication in the preceding 2 years or at any time for treatment of prostate cancer.
• \. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
• \. Men must have been surgically sterilised or use a barrier method of contraception.
• \. Pre-existing retinopathy, keratopathy or other ocular pathologies that, in the opinion of an ophthalmologist would put the patient at risk of hydroxychloroquine induced retinopathy 11. History of cardiac failure or recent history if ischaemic heart disease (\<2 years)

Sponsors & Collaborators

• St Vincent's Hospital, Sydney: lead

Study Sites (1)

St Vincent's Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Related Publications (2)

• Suzman DL, Antonarakis ES. High-dose itraconazole as a noncastrating therapy for a patient with biochemically recurrent prostate cancer. Clin Genitourin Cancer. 2014 Apr;12(2):e51-3. doi: 10.1016/j.clgc.2013.11.015. Epub 2013 Nov 14. No abstract available.

  PMID: 24332506 BACKGROUND

• Farrow JM, Yang JC, Evans CP. Autophagy as a modulator and target in prostate cancer. Nat Rev Urol. 2014 Sep;11(9):508-16. doi: 10.1038/nrurol.2014.196. Epub 2014 Aug 19.

  PMID: 25134829 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Hydroxychloroquine

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Anthony Joshua, MBBS(Hons) PhD

  St Vincent's Hospital, Sydney

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Medical Oncology, The Kinghorn Cancer Centre

Model Details: Phase I intra-patient dose escalation study Phase II Simon 2-stage cohort expansion

Study Record Dates

• First Submitted: April 17, 2018
• First Posted: May 1, 2018
• Study Start: August 23, 2018
• Primary Completion: August 30, 2023
• Study Completion: October 30, 2023
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)