Darolutamide for Salivary Gland Cancer

Not currently recruiting at 30 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Androgen inhibitors, GnRH agonists

Must not be taking: P-gp inducers, CYP3A inducers

Disqualifiers: Vascular events, Allergic reactions, 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: 3

Duration: Up to 1 year

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining two drugs, darolutamide (which blocks androgens) and leuprolide acetate (which reduces hormone levels), against a specific type of salivary gland cancer. This cancer, influenced by androgens (male hormones), has either spread, cannot be surgically removed, or has recurred after previous treatment. Suitable candidates for this trial have androgen receptor-positive salivary gland cancer that is metastatic, inoperable, or recurrent. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but it does exclude patients on certain medications that interact with the trial drugs. It's important to discuss your current medications with the trial team to ensure there are no interactions.

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

Research shows that darolutamide is usually easy for patients to handle. Earlier studies found it safe for people with a type of salivary gland cancer that responds to hormones. While some side effects occurred, most were not severe.

Leuprolide acetate is another treatment used safely for other cancers, such as prostate cancer. Studies suggest it is generally tolerable, but its long-term safety remains uncertain, and some unexpected side effects have been reported.

These treatments work together to stop or slow cancer growth by affecting hormones. Although side effects can occur, research suggests they are usually manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for salivary gland cancer focus on surgery, radiation, or chemotherapy to remove or destroy cancer cells. But darolutamide offers a novel approach by specifically targeting androgen receptors, which are often involved in the growth of certain cancer cells. Researchers are excited about darolutamide because it potentially provides a more targeted treatment option, reducing the need for more aggressive treatments that can come with significant side effects. Additionally, combining it with leuprolide acetate, a hormone therapy, might enhance its effectiveness by further suppressing cancer cell growth through hormone regulation. This dual-action strategy could make a significant difference in improving patient outcomes.

What evidence suggests that darolutamide and leuprolide acetate might be effective treatments for salivary gland cancer?

Research shows that darolutamide may help treat a type of salivary gland cancer that relies on androgen receptors. In previous studies, darolutamide controlled the disease in about 58% of cases, stopping cancer growth in more than half of the patients. It blocks androgen receptors, proteins that can promote cancer growth, especially in prostate cancer.

In this trial, participants will receive a combination of darolutamide and leuprolide acetate. In similar situations, leuprolide acetate combined with another drug showed a response rate of 41.7%. It works by lowering hormone levels that can fuel cancer growth. Together, darolutamide and leuprolide acetate might effectively treat patients whose tumors need androgens to grow. ^{1 2 3 4 6}

Who Is on the Research Team?

Alan L Ho, MD, PhD

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

Adults with advanced salivary gland cancer that has spread, can't be surgically removed, or has returned after treatment. Participants must have tumors responsive to androgen (a male hormone), measurable disease, acceptable organ function, no prior androgen-targeted therapy (except under certain conditions), and an ECOG performance status of <=2. They should not have severe heart issues or other illnesses that could affect the trial's safety.

Inclusion Criteria

I have had treatment for brain metastases.

Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (exception: patients with elevated bilirubin due to Gilbert's disease would be eligible for the trial)

My tumor can be safely biopsied.

Exclusion Criteria

Patients with uncontrolled intercurrent illness

Patients who are receiving any other investigational agents

I have had a stroke or heart attack in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive darolutamide orally twice daily and leuprolide acetate intramuscularly every 4 or 12 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 1 year

Monthly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3-6 months for 2 years or until death.

2 years

Every 3-6 months

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide
• Leuprolide Acetate

Trial Overview

The trial is testing darolutamide combined with leuprolide acetate in patients with salivary gland cancer driven by androgens. Darolutamide blocks the effects of androgens on cancer cells while leuprolide decreases hormone levels in the body. The goal is to see if this combination can stop tumor growth or shrink them.

How Is the Trial Designed?

Group I: Treatment (darolutamide, leuprolide acetate) Experimental Treatment 6 Interventions

Patients receive darolutamide PO BID on days 1-28 of each cycle and leuprolide acetate IM every 4 or 12 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy, collection of blood samples, and CT/MRI throughout the trial.

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+

Published Research Related to This Trial

In a phase 3 trial involving 1509 men with nonmetastatic, castration-resistant prostate cancer, darolutamide significantly improved metastasis-free survival, with a median of 40.4 months compared to 18.4 months for placebo (hazard ratio 0.41).

The safety profile of darolutamide was comparable to placebo, with similar rates of adverse events and no increased risk of serious side effects like seizures or cognitive disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. Fizazi, K., Shore, N., Tammela, TL., et al.[2022]

In a phase 3 trial with 1306 patients suffering from metastatic, hormone-sensitive prostate cancer, the addition of darolutamide to standard treatment significantly reduced the risk of death by 32.5% compared to placebo, indicating its efficacy in improving overall survival.

The safety profile of darolutamide was comparable to placebo, with similar rates of adverse events, suggesting that it can be safely combined with androgen-deprivation therapy and docetaxel without increasing the risk of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. Smith, MR., Hussain, M., Saad, F., et al.[2023]

Darolutamide is a promising second-generation androgen receptor inhibitor that effectively targets Enzalutamide-resistant prostate cancer cells, showing significant anti-tumor activity in various studies, including in vitro and clinical trials.

Unlike Enzalutamide, Darolutamide does not cross the blood-brain barrier, which reduces the risk of seizures, and it has been well tolerated by patients, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide as a Second-Generation Androgen Receptor Inhibitor in the Treatment of Prostate Cancer. Abbasi, A., Movahedpour, A., Amiri, A., et al.[2021]

In a phase 3 trial involving 1509 men with nonmetastatic, castration-resistant prostate cancer, darolutamide significantly improved median metastasis-free survival (40.4 months) compared to placebo (18.4 months).

At 3 years, overall survival was 83% in the darolutamide group versus 77% in the placebo group, with a 31% lower risk of death for those receiving darolutamide, while the incidence of adverse events was similar between both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. Fizazi, K., Shore, N., Tammela, TL., et al.[2021]

In the phase 3 ARAMIS trial, darolutamide significantly improved metastasis-free survival and overall survival in men with non-metastatic castration-resistant prostate cancer compared to placebo, indicating its efficacy when combined with ongoing androgen deprivation therapy.

Darolutamide was generally well tolerated, showing a low risk of central nervous system-related side effects, which is a common concern with other second-generation androgen receptor inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. Scott, LJ.[2022]

Darolutamide (NUBEQA™) is a new non-steroidal androgen receptor antagonist approved for treating non-metastatic castration-resistant prostate cancer in men, based on positive results from the phase III ARAMIS trial.

The approval of darolutamide marks a significant milestone in prostate cancer treatment, highlighting its efficacy and safety profile as demonstrated in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: First Approval. Markham, A., Duggan, S.[2020]

Darolutamide, an oral androgen receptor inhibitor, significantly improves overall survival in patients with metastatic hormone-sensitive prostate cancer when combined with androgen deprivation therapy and docetaxel, compared to placebo.

The treatment with darolutamide has a manageable safety profile, with adverse events aligning with those typically seen in androgen deprivation therapy and docetaxel, making it a viable option for patients with high-volume disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide: A Review in Metastatic Hormone-Sensitive Prostate Cancer. Lee, A.[2023]

In a 6-month study involving 117 patients with prostate cancer, the 3-month subcutaneous depot of leuprolide acetate (LA-2550) effectively suppressed serum testosterone levels to below 50 ng/dl in 98% of patients by day 28, and all patients achieved this level by day 35.

The treatment was well-tolerated, with no flare reactions and minimal adverse effects, primarily mild to moderate hot flashes, indicating a favorable safety profile while achieving significant reductions in testosterone and prostate-specific antigen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. Chu, FM., Jayson, M., Dineen, MK., et al.[2023]

Darolutamide, a novel nonsteroidal androgen receptor antagonist, has shown a favorable safety profile and significant antitumor activity in early trials for patients with metastatic castration-resistant prostate cancer (CRPC).

Ongoing phase III trials, such as ARAMIS and ARASENS, are evaluating darolutamide's effectiveness in improving metastasis-free survival and overall survival when combined with standard androgen deprivation therapy and docetaxel in men with high-risk nonmetastatic and metastatic hormone-sensitive prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer. Fizazi, K., Smith, MR., Tombal, B.[2019]

Citations

1.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6007

Darolutamide plus goserelin for androgen receptor-positive ...

In the monotherapy phase, darolutamide showed an objective response rate (ORR) of 20.8% as determined by independent central review (ICR) with ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05694819?term=AREA%5BSponsorSearch%5D(COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22Bayer%20Yakuhin,%20Ltd.%22))&rank=1

Darolutamide in Patients With Androgen Receptor-Positive ...

Moreover, this study will evaluate the safety and efficacy of Darolutamide and Goserelin combination in patients with androgen receptor-positive salivary gland ...

3.

cancernetwork.com

cancernetwork.com/view/darolutamide-shows-potential-in-treating-ar-positive-salivary-gland-cancer

Darolutamide Shows Potential in Treating AR-Positive ...

With no standard treatment available, darolutamide shows potential activity among patients with androgen receptor–positive salivary gland cancer in the phase 2 ...

4.

asco.org

asco.org/abstracts-presentations/ABSTRACT410290

The results of phase 2 study of darolutamide monotherapy.

CBR and DCR were 41.7% (95% CI 22.1–63.4) and 58.3% (95% CI 36.6–77.9), respectably. Median PFS and OS were 5.7 months (95% CI, 1.9–15.2) and not reached (95% ...

5.

withpower.com

withpower.com/trial/phase-2-carcinoma-11-2022-d882d

Darolutamide for Salivary Gland Cancer

Darolutamide has been shown to be effective in treating prostate cancer by blocking androgen receptors, which are proteins that can promote cancer growth.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05669664

Testing the Anti-cancer Drug Darolutamide in Patients With ...

This phase II trial tests how well darolutamide and leuprolide acetate work in treating patients with androgen receptor positive salivary cancer that has ...