A Study of the Safety, Tolerability and Effectiveness of Hydroxychloroquine and Itraconazole in Platinum-resistant Epithelial Ovarian Cancer

Phase 1

Completed

• Conditions: Platinum-resistant Epithelial Ovarian Cancer
• Interventions: Drug: Hydroxychloroquine; Drug: Itraconazole

• Registration Number: NCT03081702
• Lead Sponsor: University Health Network, Toronto

Brief Summary

This is a phase I/II study to find the highest dose of hydroxychloroquine that can be given safely with itraconazole in patients with advanced platinum-resistant epithelial ovarian cancer. The study will also determine the safety, tolerability, and initially determine whether the combination is useful in the treatment of patients with advanced platinum-resistant epithelial ovarian cancer.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-03-10
• Study First Submitted QC: 2017-03-10
• Study First Posted: 2017-03-16
• Study Start: 2017-07-25
• Primary Completion: 2019-08-27
• Study Completion: 2019-08-27
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-01
• Last Update Posted: 2021-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 13

Inclusion Criteria

• Aged 18 years or older.
• Histologically or cytologically confirmed epithelial ovarian cancer.
• Platinum-resistant or refractory disease defined as a radiological or clinical progression less than six months after having finished platinum-based chemotherapy.
• ECOG performance status equal to or less than 1.
• Have clinically or radiographically documented measurable disease.
• All systemic therapy must have been completed 4 weeks or greater prior to enrollment with radiologic evidence of radiological disease progression.
• Life expectancy should be more than 3 months.
• Receiving any medications or substances that are inhibitors or inducers of CYP3A4 are ineligible.
• Acceptable laboratory requirements within 7 days prior to enrollment
• Treated and asymptomatic brain metastases are eligible. Patients that received palliative radiation (for brain metastases) are eligible if they have been asymptomatic for at least 2 weeks with use of maintenance steroid therapy, and last received radiation at least 4 weeks prior to start of therapy.
• Have the ability to understand and willing to sign a written informed consent document.

Exclusion Criteria

• Have not recovered (grade 1 or less) from adverse events related to previous treatments are excluded with the exception of alopecia and lymphopenia. Peripheral sensory neuropathy must be at grade 2 or less.
• Have any other prior malignancy from which the patient has been disease free for less than 3 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of any site or any other cancer.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to itraconazole or hydroxychloroquine.
• Known G6PD deficiency due to the risk of hemolytic anemia with the use of hydroxychloroquine.
• Known retinopathy due to the risk of worsening retinopathy with hydroxychloroquine.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic or asymptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Chronic Hepatitis B or hepatitis C infections should be excluded because of potential effects on hepatic function and/ or drug interactions.
• Human Immunodeficiency Virus (HIV) infection.
• Already have a clinical indication for treatment with itraconazole (e.g. chronic candidiasis or other fungal infection) or hydroxychloroquine (e.g. lupus).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hydroxychloroquine and Itraconazole	Hydroxychloroquine	Hydroxychloroquine, orally (by mouth), at a dose of 100 mg, 200 mg, 400 mg, or 600 mg, twice a day, every day. Itraconazole, orally (by mouth) at 300 mg, twice a day, every day.
Hydroxychloroquine and Itraconazole	Itraconazole	Hydroxychloroquine, orally (by mouth), at a dose of 100 mg, 200 mg, 400 mg, or 600 mg, twice a day, every day. Itraconazole, orally (by mouth) at 300 mg, twice a day, every day.

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of hydroxychloroquine	5 years	Highest dose of hydroxychloroquine that is safe and tolerable that can be given in combination with itraconazole.

Secondary Outcome Measures

Name	Time	Method
Overall response rate	5 years	Proportion of patients achieving complete response or partial response.
Median progression-free survival	5 years	Median duration of time from start of treatment to time of progression or death.

Trial Locations

Locations (1)

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada