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

• ClinicalTrials.gov Identifier: NCT03081702
• Recruitment Status: Active, not recruiting
• First Posted: March 16, 2017
• Last Update Posted: October 28, 2019
• Sponsor: University Health Network, Toronto
• Information provided by (Responsible Party): University Health Network, Toronto

Tracking Information

• First Submitted Date: March 10, 2017
• First Posted Date: March 16, 2017
• Last Update Posted Date: October 28, 2019
• Actual Study Start Date: July 25, 2017
• Estimated Primary Completion Date: May 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 10, 2017)

Maximum tolerated dose of hydroxychloroquine [ Time Frame: 5 years ]

Highest dose of hydroxychloroquine that is safe and tolerable that can be given in combination with itraconazole.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 10, 2017)

• Median progression-free survival [ Time Frame: 5 years ]
  Median duration of time from start of treatment to time of progression or death.
• Overall response rate [ Time Frame: 5 years ]
  Proportion of patients achieving complete response or partial response.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of the Safety, Tolerability and Effectiveness of Hydroxychloroquine and Itraconazole in Platinum-resistant Epithelial Ovarian Cancer
• Official Title: A Phase I/II Trial Investigating the Tolerability, Toxicity and Efficacy of Hydroxychloroquine and Itraconazole in Patients With Advanced Platinum-resistant Epithelial Ovarian Cancer (EOC) (HYDRA-1 Study)
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Platinum-resistant Epithelial Ovarian Cancer

Intervention

• Drug: Hydroxychloroquine
  Hydroxychloroquine is approved/used for the treatment of rheumatoid arthritis, and discoid and systemic lupus erythematosus, as well as suppressive treatment and treatment of acute attacks of malaria.
• Drug: Itraconazole
  Itraconazole is approved and used for the treatment of certain systemic fungal infections.

Study Arms

Experimental: Hydroxychloroquine and 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.

Interventions:

• Drug: Hydroxychloroquine
• Drug: Itraconazole

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: March 10, 2017): 52
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 1, 2022
• Estimated Primary Completion Date: May 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT03081702
• Other Study ID Numbers: HYDRA-1
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: University Health Network, Toronto
• Study Sponsor: University Health Network, Toronto
• Collaborators: Not Provided

Investigators

• Principal Investigator: Stephanie Lheureux, M.D.; Princess Margaret Cancer Centre

• PRS Account: University Health Network, Toronto
• Verification Date: October 2019