Prostate Cancer > Darolutamide

Gedatolisib + Darolutamide for Prostate Cancer

Recruiting in Palo Alto (17 mi)

+13 other locations

Age: 18+

Sex: Male

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Celcuity Inc

No Placebo Group

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.

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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.

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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.

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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

My prostate cancer is mainly adenocarcinoma without significant neuroendocrine features.

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.

I am on hormone therapy for cancer and have not had both testicles removed.

I am a man and I am 18 years old or older.

My prostate cancer has spread and is not responding to hormone therapy.

My metastatic disease was confirmed by CT, MRI, or bone scan.

My prostate cancer is worsening despite treatment.

Exclusion Criteria

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.

I cannot absorb pills due to my stomach or bowel problems.

I have a history of serious heart problems.

I have untreated brain or spinal cord cancer spread.

My diabetes is not under control.

I cannot swallow pills.

Participant Groups

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.

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, Australia 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

🇦🇺 Approved in Australia as Nubeqa for:

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

Find A Clinic Near You

Research locations nearby Select from list below to view details:

Barbara Ann Karmanos Cancer Institute Detroit, MI

Who is running the clinical trial?

Celcuity Inc Lead Sponsor

References

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

Darolutamide: A Review in Non-Metastatic Castration-Resistant Prostate Cancer. [2022] Oral darolutamide (Nubeqa™) is a novel second-generation, nonsteroidal, selective androgen receptor (AR) inhibitor indicated for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). In the pivotal multinational, phase 3 ARAMIS trial in men with nmCRPC, relative to placebo plus ongoing androgen deprivation therapy (ADT), darolutamide (+ ADT) significantly prolonged metastasis-free survival (MFS) at the time of the primary analysis and overall survival (OS) at the time of the final OS analysis and was generally well tolerated in extended follow-up. Albeit long-term data from the real-world setting are required to fully define the safety profile of darolutamide, current evidence from the final ARAMIS analysis indicates that darolutamide has a low propensity for CNS-related adverse events (AEs) associated with other currently approved second-generation AR inhibitors. Given the efficacy and safety evidence from the final ARAMIS analysis and the key role of second-generation AR inhibitors in the management of nmCRPC, darolutamide + ADT represents an important emerging option for the treatment of men with nmCRPC who are at high risk of developing metastatic prostate cancer.

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

Darolutamide For Castration-Resistant Prostate Cancer. [2020] The treatment landscape of advanced prostate cancer continues to evolve rapidly, with newer and more active drugs being used in earlier phases of the disease based on improved overall survival. After adoption of docetaxel for metastatic castration-sensitive disease, large trials with next-generation androgen receptor-signaling inhibitors (abiraterone, enzalutamide and apalutamide) have demonstrate significant improvements in survival and important secondary endpoints. For non-metastatic castration-resistant prostate cancer, recent phase III placebo-controlled trials with enzalutamide, apalutamide and darolutamide all demonstrated benefits in improving metastasis-free survival. This review aims to summarize the clinical development of darolutamide, a novel next-generation androgen receptor antagonist, including preclinical data, clinical studies and the potential of darolutamide for the treatment of advanced prostate cancer. To date, darolutamide efficacy and tolerability has been demonstrated in the ARAMIS trial, which demonstrated an improvement in metastasis-free survival compared to placebo for non-metastatic castration-resistant prostate cancer patients with a rapid PSA doubling time. Ongoing studies will further evaluate the role of darolutamide in metastatic castration-sensitive prostate cancer in combination with docetaxel (ARASENS trial) and also in other stages of the disease.

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

Darolutamide: First Approval. [2020] Darolutamide (NUBEQA™) is a structurally distinct non-steroidal androgen receptor antagonist being developed by Orion and Bayer as a treatment for prostate cancer. Based on positive results in the phase III ARAMIS trial, darolutamide was recently approved in the USA for the treatment of men with non-metastatic castration-resistant prostate cancer. This article summarizes the milestones in the development of darolutamide leading to this first approval.

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

Darolutamide: A Review in Metastatic Hormone-Sensitive Prostate Cancer. [2023] Darolutamide (NUBEQA®) is an oral androgen receptor inhibitor (ARi) that is approved for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT) and docetaxel. In a pivotal trial, darolutamide plus ADT and docetaxel was superior to placebo plus ADT and docetaxel in prolonging the primary endpoint of overall survival, with improvements also reported in most secondary endpoints. Treatment with darolutamide plus ADT and docetaxel was associated with a manageable tolerability profile. Furthermore, the adverse events reported with darolutamide plus ADT and docetaxel were generally consistent with the safety profiles previously reported for ADT and docetaxel. Darolutamide expands the availability of treatment options in mHSPC and may be useful as a treatment for high-volume disease (typically defined as ≥ 4 bone metastases with spread outside of the pelvis and vertebral column).

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

Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. [2022] Darolutamide is a structurally unique androgen-receptor antagonist that is under development for the treatment of prostate cancer. We evaluated the efficacy of darolutamide for delaying metastasis and death in men with nonmetastatic, castration-resistant prostate cancer.

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] This trial assessed the safety, pharmacokinetics, and efficacy of darolutamide (ODM-201), a new-generation nonsteroidal androgen receptor antagonist, in Japanese patients with metastatic castration-resistant prostate cancer (mCRPC).

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] Darolutamide and enzalutamide are second-generation androgen receptor inhibitors with activity in men with castrate-resistant prostate cancer (CRPC) and different toxicity profiles.

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

Clinical Pharmacokinetics and Pharmacodynamics of the Next Generation Androgen Receptor Inhibitor-Darolutamide. [2023] Darolutamide is a next-generation androgen receptor signaling inhibitor (ARSI) currently approved for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone sensitive prostate cancer (mHSPC). Studies suggest that darolutamide also has the potential to be used to treat other stages of prostate cancer (PC), suggesting that its indications will broaden in the near future. Since ARSIs show similar efficacy for the treatment of PC, pharmacokinetic properties of these drugs and patient characteristics could help physicians decide which drug to select. This review provides an overview of the pharmacokinetic and pharmacodynamic properties of darolutamide. One of the most important pharmacological advantages of darolutamide is its low brain distribution and therefore limited seizure potential and central nervous system adverse effects. In addition, darolutamide has little drug-drug interaction potential and is unlikely to alter the exposure of other cytochrome P450 or P-glycoprotein substrates. Nevertheless, it may significantly increase the exposure of breast cancer resistant protein (BCRP) substrates. The limited solubility and bioavailability of darolutamide increases when taken together with food, regardless of the fat content. Darolutamide is excessively metabolized by oxidation and glucuronidation and excreted in the urine and feces. For this reason, dose reduction is required in patients with moderate and severe renal or severe hepatic impairment. Although no exposure-response relationship was observed with darolutamide, less advanced stages of PC showed better PSA response on treatment. Overall, darolutamide has some advantageous pharmacological properties that may lead to its preferred use, when broader registered, in selected patients across different disease stages.