Clinical trial NCT03081702: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Platinum-resistant Epithelial Ovarian Cancer
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2017-03-16
Enrollment: 13
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Maximum tolerated dose of hydroxychloroquine
timeFrame: 5 years
Secondary outcomes:
measure: Median progression-free survival
timeFrame: 5 years
measure: Overall response rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Stephanie Lheureux, M.D.
role: PRINCIPAL_INVESTIGATOR
References: