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Phase 1Recruiting

Comparing 5 approaches for metastatic hormone-sensitive prostate cancer (mhspc)

Official title: TulmiSTAR-02: A Phase I/II Open-label Study of Tulmimetostat in Combination With Darolutamide vs. Darolutamide, and Tulmimetostat With Abiraterone in Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC)

TulmiSTAR-02: A Two-part Phase I Dose Escalation Study of Tulmimetostat (DZR123) in Combination With Darolutamide or Abiraterone Followed by Open-label, Randomized, Phase II Dose Expansion Study to Assess the Safety and Efficacy of Tulmimetostat in Combination With Darolutamide Versus Darolutamide Alone in Patients With Metastatic Hormone-sensitive Prostate Cancer

Condition: Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)Sponsor: Novartis PharmaceuticalsTarget enrollment: 181

Phase 1
5 groups
One site, in Montreal
Recruiting

Interventions (5)

Medication
Tulmimetostat
Tulmimetostat is an oral dual EZH1/EZH2 inhibitor administered once daily. In Phase I, escalating dose levels will be evaluated in combination with darolutamide or abiraterone. In Phase II, one or two dose levels selected from Phase I will be evaluated in combination with darolutamide.
Medication
Darolutamide
Darolutamide 600 mg administered orally twice daily (BID).
Medication
Abiraterone
Abiraterone 1000 mg administered orally once daily (QD) in combination with prednisone/prednisolone according to local prescribing information.
Medication
Prednisone/Prednisolone
Oral corticosteroid administered with abiraterone in Phase I Group B according to local prescribing information.
Medication
Androgen Deprivation Therapy (ADT)
Background therapy consisting of a gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior orchiectomy to maintain castrate testosterone levels (\<50 ng/dL \[\<1.7 nmol/L\]). All participants will continue ADT throughout study participation.

Canadian Sites (1)

1 of 1 recruiting

Novartis Investigative Site
Montreal, Quebec
Recruiting

See who this study is looking for32 criteria

The trial’s own eligibility text, word for word from the registry. Only the trial site can say who takes part.

Inclusion

+Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
+Evidence of insufficient PSA control or suboptimal PSA response, defined as PSA ≥ 0.2 ng/mL after 6-12 months ADT and no more than 4 months of current ARPI therapy in mHSPC with declining or stable PSA trend. Eligibility based on biochemical progression should be supported by objective evidence (e.g. PSA results).
+Adult men ≥ 18 years old with de novo or recurrent mHSPC (without neuroendocrine or small cell features). The tumor lesion(s) may be located in the bone, soft tissue/visceral region, or both.
+Participants must have castrate levels of testosterone, i.e., ≤ 50 ng/dL (≤ 1.7 nM).
+Adequate bone marrow and organ function
+Prior ADT: Participants must have started ADT at least 1 month (at least 28 days) but no more than 12 months before study entry and be willing to continue ADT during treatment
+Prior taxane use for mHSPC is permitted:
+Phase I and II: Participants may have received, but not progressed on, one prior taxane-based therapy.
+Phase II: Limited to 25% participants with prior taxane use.
+Prior ARPI is allowed in both Phase I and Phase II:
+Prior ARPI use in biochemical recurrence (BCR) or curative treatment is allowed for any duration, provided therapy was discontinued and participant had no evidence of conventional imaging positive metastatic disease at that time
+Prior ARPI use in mHSPC is permitted but not mandated. If participants meet all study eligibility criteria, they are required to stop their prior ARPI after providing informed consent and remain off ARPI until Cycle 1 Day 1, when study treatment is initiated.
+Phase I: Allowed for any duration.
+Phase II: Allowed prior exposure to ARPI is ≤4 months. Participants with ongoing use of darolutamide are not eligible.
+Participants with ongoing ARPI are eligible for a switch from their ongoing ARPI therapy if they have not progressed to CRPC disease, and meet any of the criteria, indicative of suboptimal biochemical response, or intolerability, as assessed by the Investigator:
+Intolerance and non-compliance: Participant's inability to tolerate or comply with the prescribed ARPI. The site should maintain documentation to support the appropriateness of therapy changes resulting from intolerance or non-compliance.
+Other permitted prior local therapy for mHSPC:
+Phase I and II: Prior prostate-directed radiation or surgical intervention. Radiation must be completed before study entry; surgery at least 2 weeks prior.

Exclusion

−Participants with CNS metastases are excluded unless:
−Participants with evidence of mCRPC or biochemical recurrence / PSA only disease or asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy and with normal PSA for ≥ 1 year prior to the start of study treatment.
−Participants who have not received ARPI treatment for mHSPC and present with PSA levels of ≤0.5 ng/mL or those with prior/ongoing ARPI treatment presenting with PSA levels of ≤ 0.2 ng/mL prior to treatment assignment/randomization.
−they are not receiving corticosteroid for the purpose of maintaining neurologic integrity and have baseline and subsequent radiological imaging of the brain.
−Concurrent use of first-generation anti-androgens (like bicalutamide). Prior use of a first-generation anti-androgen drug in the context of ADT initiation with a GNRH analog is allowed, provided it was administered for ≤14 days and the last dose was administered ≥7 days from the study entry.
−Systemic ketoconazole is used as antineoplastic treatment for prostate cancer.
−Previous exposure to radioligand therapy.
−Treatment with any investigational agent within 28 days (or 5 half-lives, whichever is longer) prior to study entry.
−Previous treatment with any Polycomb Repressive Complex 2 (PRC2) inhibitor, including but not limited to Enhancer of Zeste Homolog 2 (EZH2) inhibitors, EZH2/1 inhibitors, or embryonic ectoderm development (EED) inhibitors.
−Herbal products that may decrease PSA levels within 4 weeks prior to the start of study drug treatment and while on study.
−Participants taking prohibited medication(s) (e.g., strong CYP3A4 inducers or strong or moderate CYP3A4 inhibitors that cannot be stopped within 7 days or 5 half-lives (whichever is longer) prior to study treatment and for the duration of the study treatment or prohibited herbal product(s) that cannot be stopped 7 days prior to study treatment.
−Have a history of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 3 years. Participants with a history of leukemia/lymphoma and/or MDS are not eligible.
−Other inclusion/exclusion criteria may apply
−they have received prior therapy (e.g. surgery, radiotherapy, gamma knife), are neurologically stable and asymptomatic.

5 concepts to explore on this page · up to 1,300 pointsTap any term to learn what it means.

In plain language

Assembled directly from this trial’s registry record. Every sentence traces to a field below — nothing here is generated or interpreted.

Learning

What this study is

This study is testing a treatment for a condition.

Phase 1/2 — a combined study that starts with early safety and continues into what the treatment does.

From the trial registry

Built from these fields:

designModule.designInfo.primaryPurpose
designModule.phases

Who receives what

There are 5 groups in this study.

Groups A, C and D receive one or more of: Tulmimetostat, Darolutamide and Androgen Deprivation Therapy (ADT).

Registry label: A: Phase I: Group A (part 1) · C: Phase II: Arm 1 · D: Phase II: Arm 2 (Optional)

Group B receives one or more of: Tulmimetostat, Abiraterone, Prednisone/Prednisolone and Androgen Deprivation Therapy (ADT).

Registry label: B: Phase I: Group B (part 2)

Group E, the comparison group, receives one or more of: Darolutamide and Androgen Deprivation Therapy (ADT).

Registry label: E: Phase II: Arm 3 (Control)

From the trial registry

Built from these fields:

armsInterventionsModule.armGroups[].label
armsInterventionsModule.armGroups[].type
armsInterventionsModule.armGroups[].interventionNames

How the study is run

Which group you would be placed in is decided by chance, like a coin flip — not by you and not by your doctor.

You, the study team, the people giving the treatment, and the people analysing the results would all be kept unaware of which group you are in until the study ends.

From the trial registry

Built from these fields:

designModule.designInfo.allocation
designModule.designInfo.maskingInfo.masking

Is there a placebo?

This study does not list a placebo group.

One group receives an existing treatment, so the two can be compared.

From the trial registry

Built from these fields:

armsInterventionsModule.armGroups[].type
armsInterventionsModule.armGroups[].interventionNames

Who the study is looking for

The study lists a minimum age of 18 years, with no upper limit given.

The study lists male participants only.

The study does not accept healthy volunteers.

These are the criteria the study lists. Only the trial site can decide whether someone can take part.

From the trial registry

Built from these fields:

eligibilityModule.minimumAge
eligibilityModule.sex
eligibilityModule.healthyVolunteers

How big and how long

The study aims to enrol about 181 people.

The study is currently expected to finish around August 2032.

The main measurement is taken over: From the first dose of study treatment through the end of Cycle 1, up to 28 days.

From the trial registry

Built from these fields:

designModule.enrollmentInfo.count
statusModule.completionDateStruct.date
outcomesModule.primaryOutcomes[].timeFrame

What the study measures

Phase I (Group A and Group B): Dose-limiting toxicities (DLTs) — measured over From the first dose of study treatment through the end of Cycle 1, up to 28 days.

Phase I (Group A and Group B): Incidence rate of Adverse Events (AEs) and Serious Adverse Events (SAEs) — measured over From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months.

Phase I (Group A and Group B): Number of Participants with dose adjustments — measured over From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months.

Phase I (Group A and Group B): Dose Intensity — measured over From the first dose of study treatment through the 30-day safety follow-up, assessed up to approximately 79 months.

The study lists 2 further main measurements.

From the trial registry

Built from these fields:

outcomesModule.primaryOutcomes[].measure
outcomesModule.primaryOutcomes[].timeFrame

Source: NCT07190300 on ClinicalTrials.gov. The full registry text is further down this page — this summary never replaces it.

Not medical advice. What do these terms mean?

What is being tested — in plain terms

About TulmimetostatDrug

Tulmimetostat is an oral dual EZH1/EZH2 inhibitor administered once daily. In Phase I, escalating dose levels will be evaluated in combination with darolutamide or abiraterone. In Phase II, one or two dose levels selected from Phase I will be evaluated in combination with darolutamide.