Metastatic Castration-resistant Prostate CancerPhase 1/2NCT05917470
A Clinical Study of ONCT-534 in Subjects With Metastatic Castration-resistant Prostate Cancer.
A Phase 1/2 study testing ONCT-534 in people with Metastatic Castration-resistant Prostate Cancer, run by Oncternal Therapeutics, Inc at 10 sites in 2 countries.
Trial summary
A first-in-human clinical trial to test the investigational treatment ONCT-534 in participants with metastatic castration-resistant prostate cancer. The main questions it aims to answer are: What are the most tolerable doses of ONCT-534? (Phase 1) Does ONCT-534 have anti-tumor activity at tolerable doses? (Phase 2)… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castration-resistant Prostate Cancer
- What is being tested?
- ONCT-534
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 20 Sep 2023to 12 Sep 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is ≥18 years of age
- Subject has histologically documented metastatic adenocarcinoma of the prostate confirmed by biopsy without neuroendocrine differentiation or small cell features.
- Subjects has a history of metastatic CRPC.
- Subject has R/R disease following treatment with at least one next-generation AR-signaling inhibitor.
- Subject has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or evaluable bony disease. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
- Subject has an Eastern Cooperative Oncology Group performance status of 0,1 or 2, and life expectancy of ≥ 6 months.
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- Subject agrees to take or continue luteinizing hormone-releasing hormone agonist or antagonist therapy or has undergone bilateral orchiectomy.
- At least 2 weeks or five half-lives have elapsed, whichever is earliest, since last systemic therapy, including taxanes or other chemotherapy. At least one month has elapsed since systemic therapy with radionuclide pharmaceutical agents
- Subject has evidence of disease progression on or after their most recent systemic treatment
- Subject has a PSA level ≥ 10 ng/mL, or ≥ 2 ng/mL and ≥ 50% increase from nadir on prior therapy, whichever is lowest.
- Subject has serum testosterone < 50 ng/dL.
- Subject has adequate renal, hepatic, and pulmonary function
- Subject is committed to practice true abstinence, or use a highly effective method of contraception with any female partner of childbearing potential unless documented to be surgically sterile (i.e., vasectomy or bilateral orchiectomy) and to not make semen donations during the study and for 3 months after the last dose of study drug.
Who cannot join
- Subject has small cell prostate cancer or neuroendocrine disease histology, including mixed histology.
- Subject has metastases to the brain or central nervous system
- Subject is receiving concurrent anti-cancer therapy (including chemotherapy, antibody therapy, immunotherapy, cellular therapy, or other experimental therapies) except for ongoing androgen inhibiting therapy such as luteinizing hormone-releasing hormone (LHRH) agonists. Supportive non-cancer directed therapies such as bisphosphonates or denosumab are allowed.
- Subjects taking a strong inhibitor of CYP3A4 or a substrate of CYP2C9 or CYP2C19
- Subject had major surgery within 30 days prior to start of study drug.
- Subject has current, untreated pathologic long-bone fractures(s), or risk of imminent pathologic fracture(s).
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- Subject has current or imminent spinal cord compression.
- Subject has an active seizure disorder or a history of seizure disorder(s).
- Subject has evidence of active human immunodeficiency virus infection, hepatitis B virus (HBV), or hepatitis C virus (HCV)
- Subject has any other serious illness or medical condition that would interfere with study participation
- Subject has abnormal electrocardiograms (ECGs) that are clinically significant, including average QTcF > 450 ms, or a history of Torsade de Pointes.
- Subject has any infection requiring parenteral antibiotic therapy or causing fever (temperature >100.5°F or 38.1°C) within 1 week prior to first dose.
- Clinically significant other malignancy with the potential to confound study assessments, with the exception of e.g., treated cutaneous squamous cell and basal carcinomas, non-muscle invasive bladder cancer, Rai Stage 0 CLL, and adequately treated Stage 1 to 2 non-cutaneous malignancy in remission for 5 years.
- Subject is unable to comply with the protocol and/or not willing or not available for follow-up assessments
- Subject has any medical intervention or other condition which, in the opinion of the Investigator, could compromise adherence with study requirements or otherwise compromise the study's objectives.
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
NEXT Oncology
Austin, Texas, 78758
Karmanos Cancer Institute
Detroit, Michigan, 48201
Next Virginia
Fairfax, Virginia, 22031
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
Columbia University Medical Center
New York, New York, 10032
XCancer Omaha
Omaha, Nebraska, 68130
NEXT Oncology
San Antonio, Texas, 78229
University of California San Francisco
San Francisco, California, 94143
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
United Kingdom1 site
The Royal Marsden NHS Trust
Sutton, Surrey, SM2 5PT
About this study
Official title: A Phase 1/2 Study of ONCT-534 in Subjects With Metastatic Castration-Resistant Prostate Cancer
A first-in-human clinical trial to test the investigational treatment ONCT-534 in participants with metastatic castration-resistant prostate cancer. The main questions it aims to answer are:
- What are the most tolerable doses of ONCT-534? (Phase 1)
- Does ONCT-534 have anti-tumor activity at tolerable doses? (Phase 2)
This is a dose escalation and expansion study where participants will receive daily oral doses of ONCT-534.
Read the detailed description
This is a Phase 1/2 multi-center study to investigate the safety, tolerability, and anti-tumor acitivity of ONCT-534 in patients with relapsed or refractory metastatic castration-resistant prostate cancer. The study consists of 2 phases: a Phase 1 Dose Escalation and a Phase 2 Dose Expansion.
- During the dose escalation in Phase 1 a group of participants will be assigned a certain dose level. Once the dose level is considered safe, the next group will be assigned a higher dose level. The dose level may be raised or lowered depending on any safety events that occur throughout Phase 1. There will be approximately 27 participants enrolled in Phase 1. At the end of Phase 1, two dose levels will be chosen to be tested in Phase 2.
- During Phase 2, participants will be randomly assigned to 1 of the 2 dose levels chose in Phase 1. Approximately 16 participants will be enrolled in each of the 2 dose level groups, for a total of 32 participants.
- Being tested
- ONCT-534
- Keywords
- Metastatic Prostate Cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ONCT-534Drug
Also called GTx-534, UT-34
ONCT-534 is a dual-action androgen receptor inhibitor (DAARI) with a novel mechanism of action that includes inhibition of AR function and degradation of the AR protein mediated by interaction with the N-terminal domain (NTD) of the AR. ONCT-534 has demonstrated preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR alteration, including those with AR amplification, mutations in the AR ligand binding domain (LBD), and splice variants with loss of the AR LBD.
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1: 40mg QD | Experimental | 40mg of single agent ONCT-534 to be administered daily in oral tablets Receives: Drug: ONCT-534 |
| Dose Level 2: 80mg QD | Experimental | 80mg of single agent ONCT-534 to be administered daily in oral tablets Receives: Drug: ONCT-534 |
| Dose Level 3: 160mg QD | Experimental | 160mg of single agent ONCT-534 to be administered daily in oral tablets Receives: Drug: ONCT-534 |
| Dose Level 4: 300mg QD | Experimental | 300mg of single agent ONCT-534 to be administered daily in oral tablets Receives: Drug: ONCT-534 |
| Dose Level 5: 600mg QD | Experimental | 600mg of single agent ONCT-534 to be administered daily in oral tablets Receives: Drug: ONCT-534 |
| Dose Level 6: 1200 mg QD | Experimental | 1200mg of single agent ONCT-534 to be administered daily in oral tablets Receives: Drug: ONCT-534 |
| BID Dose Level 1: 160 mg BID | Experimental | 600mg of single agent ONCT-534 to be administered daily in oral tablets Receives: Drug: ONCT-534 |
| BID Dose Level 2: 300 mg BID | Experimental | 300mg of single agent ONCT-534 to be administered twice daily in oral tablets Receives: Drug: ONCT-534 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicities Through Study Day 28
Incidence of DLTs through Study Day 28
Measured: Number of Participants with Dose Limiting Toxicities Through Study Day 28
Secondary outcomes (1)
Reduction of Prostate-Specific Antigen (PSA) by More Than 50%
Proportion of patients who achieve at least a 50% drop in PSA from baseline (PSA50)
Measured: Up to 51 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2023
- Study start20 Sep 2023
- Primary completion12 Sep 2024
- Study completion12 Sep 2024
Why it stopped: Oncternal Therapeutics, Inc. announced on 12 SEP 2024 its decision to discontinue its clinical trials evaluating ONCT-534, its dual action androgen receptor inhibitor for the treatment of patients with metastatic castration resistant cancer.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncternal Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Salim Yazji, MD, Study director, Oncternal Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05917470
- Sponsor's protocol ID
- ONCT-534-101
- Status last verified
- Dec 2024
- First submitted
- 7 Jun 2023
- Last updated
- 11 Dec 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of ONCT-534 in Subjects With Metastatic Castration-Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT05917470
- Acronym / sponsor ID
- ONCT-534-101
- Keywords
- Metastatic Prostate Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Oncternal Therapeutics, Inc. announced on 12 SEP 2024 its decision to discontinue its clinical trials evaluating ONCT-534, its dual action androgen receptor inhibitor for the treatment of patients with metastatic castration resistant cancer.
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Oncternal Therapeutics, IncIndustry (pharma, biotech, devices)
- Study start
- 20 Sep 2023 (actual)
- Primary completion
- 12 Sep 2024 (actual)
- Study completion
- 12 Sep 2024 (actual)
- First posted
- 23 Jun 2023 (actual)
- Results
- Posted 11 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A first-in-human clinical trial to test the investigational treatment ONCT-534 in participants with metastatic castration-resistant prostate cancer. The main questions it aims to answer are:
- What are the most tolerable doses of ONCT-534? (Phase 1)
- Does ONCT-534 have anti-tumor activity at tolerable doses? (Phase 2)
This is a dose escalation and expansion study where participants will receive daily oral doses of ONCT-534.
Detailed description
This is a Phase 1/2 multi-center study to investigate the safety, tolerability, and anti-tumor acitivity of ONCT-534 in patients with relapsed or refractory metastatic castration-resistant prostate cancer. The study consists of 2 phases: a Phase 1 Dose Escalation and a Phase 2 Dose Expansion.
- During the dose escalation in Phase 1 a group of participants will be assigned a certain dose level. Once the dose level is considered safe, the next group will be assigned a higher dose level. The dose level may be raised or lowered depending on any safety events that occur throughout Phase 1. There will be approximately 27 participants enrolled in Phase 1. At the end of Phase 1, two dose levels will be chosen to be tested in Phase 2.
- During Phase 2, participants will be randomly assigned to 1 of the 2 dose levels chose in Phase 1. Approximately 16 participants will be enrolled in each of the 2 dose level groups, for a total of 32 participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1: 40mg QD | Experimental | Drug: ONCT-53440mg of single agent ONCT-534 to be administered daily in oral tablets |
| Dose Level 2: 80mg QD | Experimental | Drug: ONCT-53480mg of single agent ONCT-534 to be administered daily in oral tablets |
| Dose Level 3: 160mg QD | Experimental | Drug: ONCT-534160mg of single agent ONCT-534 to be administered daily in oral tablets |
| Dose Level 4: 300mg QD | Experimental | Drug: ONCT-534300mg of single agent ONCT-534 to be administered daily in oral tablets |
| Dose Level 5: 600mg QD | Experimental | Drug: ONCT-534600mg of single agent ONCT-534 to be administered daily in oral tablets |
| Dose Level 6: 1200 mg QD | Experimental | Drug: ONCT-5341200mg of single agent ONCT-534 to be administered daily in oral tablets |
| BID Dose Level 1: 160 mg BID | Experimental | Drug: ONCT-534600mg of single agent ONCT-534 to be administered daily in oral tablets |
| BID Dose Level 2: 300 mg BID | Experimental | Drug: ONCT-534300mg of single agent ONCT-534 to be administered twice daily in oral tablets |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Subject is ≥18 years of age
- Subject has histologically documented metastatic adenocarcinoma of the prostate confirmed by biopsy without neuroendocrine differentiation or small cell features.
- Subjects has a history of metastatic CRPC.
- Subject has R/R disease following treatment with at least one next-generation AR-signaling inhibitor.
- Subject has at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or evaluable bony disease. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
Key exclusion criteria (15 listed)
- Subject has small cell prostate cancer or neuroendocrine disease histology, including mixed histology.
- Subject has metastases to the brain or central nervous system
- Subject is receiving concurrent anti-cancer therapy (including chemotherapy, antibody therapy, immunotherapy, cellular therapy, or other experimental therapies) except for ongoing androgen inhibiting therapy such as luteinizing hormone-releasing hormone (LHRH) agonists. Supportive non-cancer directed therapies such as bisphosphonates or denosumab are allowed.
- Subjects taking a strong inhibitor of CYP3A4 or a substrate of CYP2C9 or CYP2C19
- Subject had major surgery within 30 days prior to start of study drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ONCT-534Also: GTx-534, UT-34ONCT-534 is a dual-action androgen receptor inhibitor (DAARI) with a novel mechanism of action that includes inhibition of AR function and degradation of the AR protein mediated by interaction with the N-terminal domain (NTD) of the AR. ONCT-534 has demonstrated preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR alteration, including those with AR amplification, mutations in the AR ligand binding domain (LBD), and splice variants with loss of the AR LBD. | Drug | BID Dose Level 1: 160 mg BID, BID Dose Level 2: 300 mg BID, Dose Level 1: 40mg QD, Dose Level 2: 80mg QD, Dose Level 3: 160mg QD, Dose Level 4: 300mg QD, Dose Level 5: 600mg QD, Dose Level 6: 1200 mg QD |
Primary outcome
Dose Limiting Toxicities Through Study Day 28
Time frame: Number of Participants with Dose Limiting Toxicities Through Study Day 28
Incidence of DLTs through Study Day 28
1 secondary outcome
Reduction of Prostate-Specific Antigen (PSA) by More Than 50%
Time frame: Up to 51 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Metastatic Castration-resistant Prostate Cancer
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STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingPhase 2
A Study to Test Inavolisib Treatment in Participants With Metastatic Castration-Resistant Prostate Cancer
Metastatic Castration-Resistant Prostate Cancer
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Castration-resistant Prostate Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Salim Yazji, MD study director
Oncternal Therapeutics
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ONCT-534 in people with Metastatic Castration-resistant Prostate Cancer, run by Oncternal Therapeutics, Inc at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicities Through Study Day 28 (time frame: Number of Participants with Dose Limiting Toxicities Through Study Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2024.