Gedatolisib + Darolutamide for Prostate Cancer

Recruiting at 13 trial locations

Overseen By Genelle Brower, RN

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Celcuity Inc

Must be taking: LHRH analogs

Must not be taking: PI3K inhibitors, AKT inhibitors

Disqualifiers: Other malignancies, Uncontrolled diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

54 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 1/2, open-label, randomized, dose finding and dose expansion study to evaluate the safety, preliminary efficacy, and PK of gedatolisib in combination with darolutamide in subjects with mCRPC.

Will I have to stop taking my current medications?

The trial requires that you stop taking any androgen receptor inhibitors at least 4 weeks before starting the study drug. You also need to be at least 2 weeks beyond treatment with targeted therapy or major surgery, and 3 weeks beyond any other systemic anticancer therapy or radiation therapy.

What data supports the effectiveness of the drug Darolutamide for prostate cancer?

Darolutamide has been shown to significantly prolong survival in men with non-metastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer when used with other therapies, according to several clinical trials. It is generally well tolerated and has a low risk of causing central nervous system side effects. ^{1 2 3 4 5}

Is the combination of Gedatolisib and Darolutamide safe for humans?

Darolutamide, used for prostate cancer, has been generally well tolerated in trials, with a low chance of causing brain-related side effects compared to similar drugs. It has a manageable safety profile when combined with other treatments like androgen deprivation therapy and docetaxel. ^{1 3 4 6 7}

What makes the drug combination of Gedatolisib and Darolutamide unique for prostate cancer treatment?

The combination of Gedatolisib and Darolutamide is unique because Darolutamide is a next-generation androgen receptor inhibitor that has a low risk of causing central nervous system side effects, unlike other similar drugs. This makes it a potentially safer option for patients, especially when combined with Gedatolisib, which may offer additional therapeutic benefits. ^{1 3 4 5 8}

Research Team

Nadene Zack, MS

Principal Investigator

Celcuity Inc

Eligibility Criteria

This trial is for men with metastatic castration-resistant prostate cancer (mCRPC). Specific eligibility details are not provided, but typically participants would need to meet certain health standards and have no conflicting conditions.

Inclusion Criteria

I am fully active and can carry on all my pre-disease activities without restriction.

My cancer progressed despite treatment with a specific prostate cancer medication.

My prostate cancer is mainly adenocarcinoma without significant neuroendocrine features.

Exclusion Criteria

I have had cancer before, but it was either skin cancer treated successfully or another type of cancer that has been gone for over 3 years.

My prostate cancer has a small cell component with at least 10% neuroendocrine cells.

I have been treated with a PI3K, AKT, or mTOR inhibitor before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose finding to evaluate safety and determine the recommended Phase 2 dose of gedatolisib in combination with darolutamide

1 year

Weekly visits for gedatolisib administration

Phase 2 Treatment

Assessment of safety and preliminary efficacy of the recommended Phase 2 dose of gedatolisib in combination with darolutamide

6 months

Weekly visits for gedatolisib administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days post last dose

Long-term Follow-up

Assessment of radiographic progression-free survival and overall survival

24 months post Cycle 1 Day 1

Treatment Details

Interventions

• Darolutamide
• Gedatolisib

Trial Overview The study is testing the combination of two drugs, Gedatolisib and Darolutamide, in patients with mCRPC. It's an early-stage trial to find out the right doses and see how well these drugs work together.

Participant Groups

Group I: Phase 2 Experimental Treatment 2 Interventions

The recommended Phase 2 dose (RP2D) of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)

Group II: Phase 1 Arm 2 Experimental Treatment 2 Interventions

Arm 2 - 180 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)

Group III: Phase 1 Arm 1 Experimental Treatment 2 Interventions

Arm 1 - 120 mg of gedatolisib (administered once weekly for 3 weeks on/1 week off) in combination with darolutamide 600 mg (two 300 mg tablets) orally administered twice daily (equivalent to a total daily dose of 1200 mg on Days 1-28 of each cycle)

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?

Celcuity Inc

Lead Sponsor

Trials

9

Recruited

1,600+

Findings from Research

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 has shown significant efficacy in improving metastasis-free survival in patients with non-metastatic castration-resistant prostate cancer, as demonstrated in the ARAMIS trial.

The treatment landscape for advanced prostate cancer is evolving, with darolutamide being evaluated in ongoing studies for its potential benefits in combination with docetaxel for metastatic castration-sensitive prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Darolutamide For Castration-Resistant Prostate Cancer. Bastos, DA., Antonarakis, ES.[2020]

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 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]

Darolutamide, a new androgen receptor antagonist, was found to be well tolerated in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC), with most treatment-emergent adverse events being mild (Grade 1/2).

The pharmacokinetics of darolutamide showed a dose-dependent increase in drug levels, and while only 11% of patients showed a prostate-specific antigen response, the drug did not present any new safety concerns compared to Western populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of darolutamide (ODM-201): a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer. Matsubara, N., Mukai, H., Hosono, A., et al.[2023]

In a study involving 249 men with metastatic castrate-resistant prostate cancer, patient preference between darolutamide and enzalutamide was balanced, with no significant preference for either treatment (p = 0.92).

Darolutamide was associated with less fatigue and a moderate improvement in episodic memory compared to enzalutamide, suggesting it may offer a better quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. Colomba, E., Jonas, SF., Eymard, JC., et al.[2023]

Darolutamide is an effective treatment for nonmetastatic castration-resistant prostate cancer and metastatic hormone-sensitive prostate cancer, with potential for broader use in other stages of prostate cancer due to its favorable pharmacokinetic properties.

One of the key advantages of darolutamide is its low distribution to the brain, which reduces the risk of seizures and central nervous system side effects, making it a safer option compared to other androgen receptor signaling inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics and Pharmacodynamics of the Next Generation Androgen Receptor Inhibitor-Darolutamide. Podgoršek, E., Mehra, N., van Oort, IM., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

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

2. New Zealand pubmed.ncbi.nlm.nih.gov

Darolutamide For Castration-Resistant Prostate Cancer. [2020]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Darolutamide: First Approval. [2020]

4. France pubmed.ncbi.nlm.nih.gov

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

5. United States pubmed.ncbi.nlm.nih.gov

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Phase 1 study of darolutamide (ODM-201): a new-generation androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Cross-over Phase 2 Trial of Darolutamide and Enzalutamide in Men with Asymptomatic or Mildly Symptomatic Metastatic Castrate-resistant Prostate Cancer: Patient Preference and Cognitive Function in ODENZA. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetics and Pharmacodynamics of the Next Generation Androgen Receptor Inhibitor-Darolutamide. [2023]