Clinical trial NCT05272462: Oral Minoxidil for the Treatment of Recurrent Platinum Resistant Epithelial Ovarian Cancer
Official title: A Phase II Trial of Oral Minoxidil for the Treatment of Recurrent Platinum Resistant Epithelial Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Ovarian Cancer
Platinum Resistant
Epithelial Ovarian Cancer
Lead sponsor: Loyola University
Sponsor class: OTHER
Collaborators: name: Cures Within Reach
name: Medical University of South Carolina
First posted: 2022-03-09
Enrollment: 34
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a non-randomized prospective single-site trial of minoxidil for patients living with recurrent platinum resistant ovarian cancer.
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to determine the response rate of patients with recurrent platinum resistant ovarian cancer when treated with oral minoxidil. Secondary objectives include estimating the time to disease progression while on minoxidil and to describe the toxicities of minoxidil when used for patients with recurrent platinum resistant ovarian cancer. An exploratory objective is to evaluate if efficacy of minoxidil is improved in patients that have the Kir6/SUR complex versus those that do not.

Detailed description: Minoxidil is approved by the Food and Drug Administration (FDA) for treatment of hypertension. In previous studies, the sulfonylurea receptor (SUR) subunit controls the selectivity of the pharmacological response to drugs that either inhibit or stimulate the Kir6/SUR channel. Oral minoxidil acts as an activator of the Kir6/SUR2 channel upon selective binding to sulfonylurea receptor 2 (SUR2). Activation of the Kir6.2 potassium channel by minoxidil leads to potassium outflow and calcium entry which produces a cytoplasmic electrical charge that is more negative. This in turn creates an attractive force for calcium to enter the cell. Increased intracellular calcium disrupts mechanisms of cell division by arresting the cell cycle in G2/M phase and this is associated with alteration of the oxidative state, disruption of the mitochondria and activation of the caspase-3-independent cell death pathway.

Evaluation of arrest of tumor growth was evaluated in a previous study. This was done in vitro as well as in vivo by establishing a xenograft model from a Kir6.2/SUR2 positive high grade serous ovarian cancer cell line. In the mice treated with minoxidil, five of the 6 mice had no evidence of measurable disease at necropsy. In contrast, the untreated mice were found to have carcinomatosis and ascites in all 6 mice, demonstrating tumor reduction with minoxidil treatment.

While recurrent ovarian cancer can be treated with a multitude of drugs, the response rates are limited. Treatment options can also be limited secondary to myelosuppression as a result of patients being heavily pretreated. Minoxidil appears to have the advantage of not causing severe myelosuppression which can limit treatment options for patients. Laboratory results provide promising evidence that minoxidil could be used for the treatment of recurrent ovarian cancer.

This study plans to conduct a single center phase II study to evaluate the efficacy and safety of oral minoxidil in the treatment of platinum resistant ovarian cancer. The primary goal is to assess whether treatment with minoxidil will reduce tumor burden in patients with recurrent ovarian cancer and have a minimal toxicity profile.

Eligibility criteria: Inclusion Criteria

* Participants must have recurrent platinum resistant ovarian cancer. Histologic documentation of the recurrence is not required.
* Participants must have platinum resistant disease defined as recurrence less than 6 months after initial platinum based treatment.
* Participants must be greater than or equal to 18 years of age.
* Participants must have an Eastern Cooperative Group (ECOG) Performance Status (PS) less than or equal to 2.
* Participants must be able to take oral medications.

Exclusion Criteria

* Participants must not have had chemotherapy or radiotherapy within 4 weeks
* Participants must not be receiving any other investigational agents.
* Participants must not have brain metastases
* Participants must not have allergic reactions to minoxidil
* Participants must not have congestive heart failure
* Participants must not have history of cardiac disease
* Participants must not have uncontrolled hypertension
* Participants must not be on dialysis

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
Study officials:
affiliation: Loyola University
name: Margaret Liotta, DO
role: PRINCIPAL_INVESTIGATOR
References: