New Treatments for Prostate Cancer

Recruiting at 11 trial locations

Overseen By Lesley Seymour

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must be taking: LHRH agonists

Must not be taking: Systemic corticosteroids

Disqualifiers: Other malignancies, CNS involvement, cardiac disease, 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: 1

Duration: 8-12 weeks

200 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the pre-study screening is to test for DNA abnormalities or biomarkers.

Will I have to stop taking my current medications?

The trial requires that you stop taking anti-androgens at least 4 weeks before enrollment (6 weeks for bicalutamide). LHRH therapy must continue unless you have had surgical castration. The protocol does not specify other medications, so it's best to discuss with the trial team.

Is darolutamide generally safe for humans?

Darolutamide is generally well tolerated and has a low risk of causing central nervous system side effects, which are common with similar treatments. It has been approved for use in non-metastatic castration-resistant prostate cancer based on positive safety and efficacy results from clinical trials. ^{1 2 3 4 5}

What makes the drug combination including Darolutamide unique for prostate cancer treatment?

This drug combination is unique because it includes Darolutamide, a novel androgen receptor inhibitor, which has shown to improve survival in non-metastatic castration-resistant prostate cancer and is being evaluated for its potential in other stages of prostate cancer. The combination targets multiple pathways, including the androgen pathway and the immune system, offering a comprehensive approach to treatment. ^{1 4 6 7 8}

Research Team

Aaron Hansen

Principal Investigator

University Health Network, Toronto, ON, Canada

Sebastien Hotte

Principal Investigator

Juravinski Cancer Centre at Hamilton Health Sciences, Hamilton, ON Canada

Zineb Hamilou

Principal Investigator

CHUM-Centre Hospitalier de l'Universite de Montreal

Kim Chi

Principal Investigator

BCCA - Vancouver Cancer Centre

Michael Kolinsky

Principal Investigator

Cross Cancer Institute, Edmonton, AB Canada

Som Mukherjee

Principal Investigator

Juravinski Cancer Centre at Hamilton Health Sciences Centre, ON Canada

Michael Ong

Principal Investigator

Ottawa Hospital Research Institute, Ottawa, ON Canada

Eligibility Criteria

Men over 18 with advanced prostate cancer that's resistant to castration and has progressed despite treatment. They must have a life expectancy of at least 6 months, be in good physical condition (ECOG status 0 or 1), and have adequate organ function. Participants need to provide consent for blood tests and tumor sample release, agree to use effective contraception, and be available for follow-up.

Inclusion Criteria

My cancer is growing despite low testosterone levels.

I am 18 years old or older.

Patients must have radiologically documented disease

Exclusion Criteria

I will need growth factors during the trial.

I have heart problems, uncontrolled high blood pressure, or serious liver issues.

Patients with serious illnesses or medical conditions posing safety risks or hindering protocol adherence

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive treatment based on identified biomarkers, including various experimental drugs

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Adavosertib
• Carboplatin
• CFI-400945
• Darolutamide
• Durvalumab and Tremelimumab
• Ipatasertib
• Savolitinib

Trial Overview The trial is testing various drugs like Carboplatin, Durvalumab with Tremelimumab, Adavosertib, Savolitinib, Darolutamide, CFI-400945, Ipatasertib on patients whose tumors show specific DNA abnormalities or biomarkers. The goal is to see which drug works best based on these markers.

Participant Groups

Group I: novel non-steroidal androgen receptor (AR) antagonist Experimental Treatment 1 Intervention

Group II: cMET inhibitor Experimental Treatment 1 Intervention

Group III: WEE-1 inhibitor - ARM CLOSED Experimental Treatment 1 Intervention

Group IV: Ipatasertib AKT inhibitor Experimental Treatment 1 Intervention

Group V: Durvalumab and Tremelimumab immunotherapy Experimental Treatment 1 Intervention

Group VI: Carboplatin platinum based chemotherapy Experimental Treatment 1 Intervention

Group VII: CFI400945 PLK4 inhibitor - ARM CLOSED Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Canadian Cancer Clinical Trials Network

Collaborator

Trials

2

Recruited

530+

BC Cancer Foundation

Collaborator

Trials

20

Recruited

8,600+

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, an androgen receptor inhibitor, showed minimal impact on cerebral blood flow (CBF) in cognition-related brain regions, indicating a low risk of central nervous system side effects, which is beneficial for patients.

In contrast, enzalutamide significantly reduced CBF in multiple brain areas, suggesting potential cognitive risks associated with its use, highlighting the importance of considering CNS effects when choosing prostate cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial. Williams, SCR., Mazibuko, N., O'Daly, O., et al.[2023]

In a comparison of darolutamide with apalutamide and enzalutamide for treating nonmetastatic castration-resistant prostate cancer, no differences in metastasis-free survival were found, indicating similar efficacy among the treatments.

Darolutamide demonstrated a better safety profile, with significantly lower rates of falls, fractures, and rashes compared to apalutamide, and lower rates of dizziness and fatigue compared to enzalutamide, suggesting it may be a preferable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer. Halabi, S., Jiang, S., Terasawa, E., et al.[2021]

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]

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]

New hormonal therapies like abiraterone and enzalutamide have significantly changed the treatment landscape for metastatic castration-resistant prostate cancer, offering new options for patients.

With multiple new treatments in trials targeting various pathways, there is an urgent need to identify predictive markers to guide treatment sequencing and optimize patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New therapies in metastatic castration resistant prostate cancer]. Thibault, C., Massard, C.[2015]

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]

References

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

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

2. France pubmed.ncbi.nlm.nih.gov

Comparison of Cerebral Blood Flow in Regions Relevant to Cognition After Enzalutamide, Darolutamide, and Placebo in Healthy Volunteers: A Randomized Crossover Trial. [2023]

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

Indirect Comparison of Darolutamide versus Apalutamide and Enzalutamide for Nonmetastatic Castration-Resistant Prostate Cancer. [2021]

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

Darolutamide: First Approval. [2020]

5. 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]

6. France pubmed.ncbi.nlm.nih.gov

[New therapies in metastatic castration resistant prostate cancer]. [2015]

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

Darolutamide For Castration-Resistant Prostate Cancer. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Darolutamide and survival in metastatic, hormone-sensitive prostate cancer: a patient and caregiver perspective and plain language summary of the ARASENS trial. [2022]