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

• Status: Recruiting
• Trial end date: 2023-03-30
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St Vincent's Hospital, Sydney
• Treatments: Hydroxychloroquine; Hydroxyitraconazole; Itraconazole

Criteria

Inclusion Criteria:

1. Males ≥ 18 years of age with histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features

2. Prostate cancer initially treated by radical prostatectomy, radiotherapy (including brachytherapy) or both, with curative intent

3. PSA ≥ 1 ng/ml with at least two sequential rises at least 1 week apart according to PCWG3.

4. Serum testosterone ≥ 5 nmol/L

5. QTc ≤ 470 msec using Fridericia correction formula

6. 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

7. Adequate liver function with ALT/AST < 1.5 x ULN, bilirubin < 1.5 x ULN

8. Adequate renal function with creatinine clearance > 50 ml/min

9. ECOG Performance Status ≤ 1

10. Able to start study treatment within 28 days of consent

11. Willing and able to comply with all study requirements, including treatment (e.g. able to swallow tablets), timing and/or nature of required assessments

12. Signed, written informed consent

Exclusion Criteria:

1. 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

2. 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.

3. PSA doubling time ≤ 3 months calculated using MSKCC calculator (https://www.mskcc.org/nomograms//prostate/psa-doubling-time)

4. 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

5. Life expectancy of ≤ 1 year

6. History of another invasive cancer within 3 years before screening with the exception of fully treated cancer with remote probability of recurrence

7. Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety

8. Use of hydroxychloroquine and/or itraconazole for any indication in the preceding 2 years or at any time for treatment of prostate cancer.

8. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.

9. Men must have been surgically sterilised or use a barrier method of contraception.

10. 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)