Darolutamide + Hormone Therapy for Granulosa Cell Tumor

Not currently recruiting at 77 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Aromatase inhibitors

Must not be taking: AR inhibitors

Disqualifiers: Cardiac disease, Active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three medications—darolutamide, leuprolide acetate, and exemestane—to evaluate their effectiveness in treating ovarian granulosa cell tumors that have recurred after earlier improvement. Darolutamide, a hormone therapy, blocks hormones that can promote tumor growth. Leuprolide acetate and exemestane lower certain hormone levels in the body, potentially slowing or stopping tumor growth. The trial seeks participants with ovarian granulosa cell tumors that have returned after prior treatment and have progressed despite previous aromatase inhibitor use. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss your current medications with the trial team to get specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments in this trial have been safe in past studies. Darolutamide, which blocks certain hormones, has been well tolerated by patients with prostate cancer. It helps control the disease for a long time and is safe for extended use.

Exemestane, which reduces estrogen levels, is generally safer and more effective than similar treatments. It has been used successfully in various situations.

Leuprolide acetate also has a good safety record. Specifically, in studies, it helped 66% of patients with recurrent granulosa cell tumors, a type of ovarian tumor. These results support its safe use for these tumors.

Overall, these treatments have been used safely in other conditions and could be well-tolerated in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination because it brings a fresh approach to tackling granulosa cell tumors. While standard treatments often focus on surgery and traditional chemotherapy, this combination uses darolutamide, exemestane, and leuprolide acetate, which together offer a novel hormonal angle. Darolutamide is particularly intriguing as it targets androgen receptors, which is a different mechanism from typical cancer treatments. This combination aims to disrupt the tumor's growth signals more effectively and could potentially offer a new lifeline for patients who haven't responded well to current options.

What evidence suggests that this combination treatment could be effective for recurrent ovarian granulosa cell tumors?

This trial will evaluate the combination of darolutamide, leuprolide acetate, and exemestane for managing ovarian granulosa cell tumors. Research suggests that darolutamide blocks male hormones, stopping tumor growth. Exemestane lowers estrogen levels, which also helps slow or stop tumor growth. One study showed that leuprolide acetate controlled these tumors in 66% of cases. Together, these treatments might shrink or stabilize tumors or prevent their recurrence. ^{1 2 4 6 7}

Who Is on the Research Team?

Elizabeth Hopp

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with recurrent ovarian granulosa cell tumors who've had at least one prior treatment and have progressed on an aromatase inhibitor. They must be in good health, not pregnant or nursing, and willing to use contraception. People with certain heart conditions, infections, or other cancers that could affect the study can't join.

Inclusion Criteria

I am healthy enough to follow through with the study and its follow-ups.

I had hepatitis C but am cured, or I'm being treated with an undetectable viral load.

Patient must have measurable disease as per RECIST 1.1 criteria

Exclusion Criteria

Known hypersensitivity to the study drugs or their ingredients

I have been treated with AR inhibitors before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive exemestane orally once daily and darolutamide orally twice daily starting on days -14 to -7 prior to cycle 1, day 1, and then on days 1-28 of each cycle. Leuprolide acetate is administered intramuscularly on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 5 years

Monthly visits for treatment administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for 2 years and then every 6 months for 3 years.

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide
• Exemestane
• Leuprolide Acetate

Trial Overview The trial tests a combination of darolutamide (blocks male hormones), leuprolide acetate (lowers certain hormones), and exemestane (stops estrogen production) to see if they can slow down or stop tumor growth in patients whose ovarian cancer has returned.

How Is the Trial Designed?

Group I: Treatment (exemestane, darolutamide, leuprolide acetate) Experimental Treatment 8 Interventions

Patients receive exemestane PO QD and darolutamide PO BID starting on days -14 to -7 prior to C1D1 and then on days 1-28 of each cycle. Patients receive leuprolide acetate IM on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo chest CT or chest x-ray and CT, MRI, or PET/CT as well as blood sample collection throughout the study. Patients undergo collection of archived tissue during screening.

Darolutamide is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Nubeqa for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel

Approved in European Union as Nubeqa for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel

Approved in Canada as Nubeqa for:

• Non-metastatic castration-resistant prostate cancer (nmCRPC)
• Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06169124

NCT06169124 | Study to Test the Drug Darolutamide ... This phase II trial tests how well darolutamide in combination with leuprolide acetate and exemestane works in treating patients with ovarian granulosa cell ...

2. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06524

Study to Test the Drug Darolutamide along with ... This phase II trial tests how well darolutamide in combination with leuprolide acetate and exemestane works in treating patients with ovarian granulosa cell ...

3. nrgoncology.org nrgoncology.org/GY033

NRG-GY033: Recurrent granulosa cell tumors There is evidence that darolutamide, leuprolide acetate, and exemestane can shrink or stabilize your type of cancer. It is not possible to know now if the study ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28753851/

Safety and Antitumour Activity of ODM-201 (BAY-1841788) ... Prolonged treatment with high doses of ODM-201 was well tolerated and provided long-lasting disease control in patients with mCRPC. ODM-201 represents a ...

5. ema.europa.eu ema.europa.eu/en/documents/assessment-report/nubeqa-epar-public-assessment-report_en.pdf

Assessment report - darolutamide - EMA - European Union It included fibroadenoma of mammary glands and benign thymoma of thymus in males, benign granulosa cell tumours of ovaries in females, and ...

6. bayer.com bayer.com/en/us/news-stories/new-data-for-nubeqa

New Data for NUBEQA® Build on Safety and Efficacy ... The subgroup analysis showed that, in the low-volume (LV) subgroup, NUBEQA plus ADT reduced the risk of radiological progression or death by 70% ...

7. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer

FDA approves darolutamide for metastatic castration ... Treatment with darolutamide resulted in a statistically significant improvement in rPFS compared to placebo. Median rPFS was not reached in the ...