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

NCT ID: NCT03081702

Last Updated: 2021-04-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-25
• Study Completion Date: 2019-08-27

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.

Conditions

Platinum-resistant Epithelial Ovarian Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Hydroxychloroquine

Intervention Type: DRUG

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.

Itraconazole

Intervention Type: DRUG

Itraconazole is approved and used for the treatment of certain systemic fungal infections.

Interventions

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.

Intervention Type: DRUG

Itraconazole

Itraconazole is approved and used for the treatment of certain systemic fungal infections.

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephanie Lheureux, M.D.

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

Canada

References

Marastoni S, Madariaga A, Pesic A, Nair SN, Li ZJ, Shalev Z, Ketela T, Colombo I, Mandilaras V, Cabanero M, Bruce JP, Li X, Garg S, Wang L, Chen EX, Gill S, Dhani NC, Zhang W, Pintilie M, Bowering V, Koritzinsky M, Rottapel R, Wouters BG, Oza AM, Joshua AM, Lheureux S. Repurposing Itraconazole and Hydroxychloroquine to Target Lysosomal Homeostasis in Epithelial Ovarian Cancer. Cancer Res Commun. 2022 May 4;2(5):293-306. doi: 10.1158/2767-9764.CRC-22-0037. eCollection 2022 May.

Reference Type: DERIVED

PMID: 36875717 (View on PubMed)

Other Identifiers

HYDRA-1

Identifier Type: -

Identifier Source: org_study_id