a study of the safety, tolerability and effectiveness of hydroxychloroquine and itraconazole in platinum-resistant epithelial ovarian cancer

Conditions: Platinum-resistant Epithelial Ovarian Cancer

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).