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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03081702
Recruitment Status : Active, not recruiting
First Posted : March 16, 2017
Last Update Posted : October 28, 2019
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Platinum-resistant Epithelial Ovarian Cancer Drug: Hydroxychloroquine Drug: Itraconazole Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : July 25, 2017
Estimated Primary Completion Date : May 1, 2022
Estimated Study Completion Date : October 1, 2022

Arm Intervention/treatment
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.

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.

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Median progression-free survival [ Time Frame: 5 years ]
    Median duration of time from start of treatment to time of progression or death.

  2. Overall response rate [ Time Frame: 5 years ]
    Proportion of patients achieving complete response or partial response.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03081702

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Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
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Principal Investigator: Stephanie Lheureux, M.D. Princess Margaret Cancer Centre
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Responsible Party: University Health Network, Toronto Identifier: NCT03081702    
Other Study ID Numbers: HYDRA-1
First Posted: March 16, 2017    Key Record Dates
Last Update Posted: October 28, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents
Antifungal Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs