New Treatments for Prostate Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for prostate cancer, focusing on drugs like Adavosertib (a potential cancer treatment) and Carboplatin (a chemotherapy drug). Researchers aim to determine how these treatments perform in prostate cancer resistant to standard hormone therapies. Individuals with castration-resistant prostate cancer that has worsened despite treatment might be suitable candidates for this trial. Participants will undergo screening for specific DNA changes and biomarkers related to prostate cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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

Research has shown that adavosertib exhibits early signs of tumor-fighting capabilities, but safety concerns exist. At higher doses, patients experienced severe diarrhea and low blood cell counts, indicating poor tolerance.

Savolitinib, approved in China for lung cancer treatment, suggests safety for that condition. Studies suggest it is safe when combined with other drugs, but its effectiveness in treating prostate cancer remains under investigation.

Darolutamide is generally well tolerated for up to 25 months in prostate cancer patients. Common side effects include tiredness, skin rash, and hot flashes, with serious side effects being rare.

CFI-400945 is still under study for safety. Reports of serious side effects, such as fever and infections, exist, but data remains limited.

Ipatasertib is generally safe when used with abiraterone, a prostate cancer drug. Some patients discontinued treatment due to side effects, which were expected based on previous studies.

The combination of durvalumab and tremelimumab has shown potential in aiding the immune system to fight tumors. However, the safety of this combination is not fully understood, with some rare side effects reported.

Carboplatin is a standard chemotherapy drug with a known safety profile. It is used in various cancer treatments and is generally considered safe, though it can cause side effects like low blood counts and nausea.

Overall, while each treatment has its own safety information, potential participants should weigh both the benefits and risks before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these prostate cancer treatments because they offer innovative approaches beyond the current standards, like hormone therapy, surgery, or chemotherapy. Adavosertib is a WEE-1 inhibitor, which targets a key protein in cancer cell division, potentially halting tumor growth more effectively. CFI-400945 is a PLK4 inhibitor, aiming at a specific enzyme involved in cell cycle regulation, offering a novel route to stop cancer progression. Meanwhile, Durvalumab and Tremelimumab are immunotherapies that harness the body's immune system to target and destroy cancer cells, a promising alternative to traditional therapies. Each of these treatments brings a unique mechanism of action to the table, providing hope for more targeted and effective prostate cancer management.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research shows that several treatments in this trial may help with prostate cancer. Participants may receive Adavosertib, which studies indicate can stabilize the disease in more than half of the patients, with some experiencing tumor shrinkage. Another treatment option is Darolutamide, which has significantly extended the time patients live without the cancer worsening. Ipatasertib, also tested in this trial, lowers the risk of disease progression when used with other treatments. The combination of Durvalumab and Tremelimumab shows promise in reducing tumor size in certain prostate cancers. Lastly, Carboplatin, part of a separate treatment arm, has shown moderate effectiveness in advanced cases, with some patients responding positively. Each treatment has demonstrated some level of effectiveness in previous studies, supporting their potential in this trial. ^{1 2 3 6 7}

Who Is on the Research Team?

Michael Kolinsky

Principal Investigator

Cross Cancer Institute, Edmonton, AB Canada

Som Mukherjee

Principal Investigator

Juravinski Cancer Centre at Hamilton Health Sciences Centre, ON Canada

Kim Chi

Principal Investigator

BCCA - Vancouver Cancer Centre

Michael Ong

Principal Investigator

Ottawa Hospital Research Institute, Ottawa, ON Canada

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

Are You a Good Fit for This Trial?

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

Patients must have radiologically documented disease

Patients must meet specified blood count and chemistry criteria

My cancer is growing despite low testosterone levels.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8282703/

Safety, anti-tumor activity, and biomarker analysis in a ... We also found that adavosertib treatment increased nuclear pY15-Cdk levels at C1D8 in 4 of the 5 patients with low baseline levels (including in 3 patients who ...

2. aacrjournals.org aacrjournals.org/cancerrescommun/article/4/7/1793/746640/A-Phase-II-Trial-of-the-WEE1-Inhibitor-Adavosertib

A Phase II Trial of the WEE1 Inhibitor Adavosertib in SETD2 ... Minor tumor regressions were observed in 4/18 (22%) evaluable patients. Stable disease (SD) was the best overall response in 10/18 (56%) ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1040842825000988

WEE1 inhibition in cancer therapy: Mechanisms, synergies ... Adavosertib shows promising clinical activity in multiple solid tumors. •. Biomarkers like TP53 mutation predict response to WEE1 inhibition. Abstract.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11557630/

Adavosertib in Combination with Olaparib in Patients with ... Preclinical data demonstrate that adavosertib has the potential to both enhance the antitumor effect of PARP inhibitors such as olaparib as well ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT344345

EFFORT: EFFicacy Of adavosertib in parp ResisTance: A ... CBR (90% CI), 63% (48–76), 89% (76–96) ; Median PFS, months (90%CI), 5.5 (3.9–6.9), 6.8 (4.3–8.3) ...

6. onclive.com onclive.com/view/adavosertib-shows-early-antitumor-activity-despite-safety-concerns-in-uterine-serous-carcinoma

Adavosertib Shows Early Antitumor Activity Despite Safety ... The data showed that 10 patients achieved responses, including 1 CR, 8 confirmed PRs, and 1 unconfirmed PR, which comprised an ORR of 29.4% (95% ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-01606

ADAGIO: A Phase IIb, Open-Label, Single-Arm, Multicenter ... Adavosertib showed some antitumor activity in patients with recurrent/persistent USC. However, at 300 mg once daily dosing, it was not well tolerated in this ...