Safety, Tolerability and Pharmacokinetics of ONC1-0013B in Patients With Progressive Metastatic Castration-resistant Prostate Cancer

Study Overview
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Brief Summary
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This is a PhaseI, open-label study, Dose-Escalation Study, where tolerated doses will be escalated to the next doses with the safety, tolerability, and PK being evaluated in metastatic castration-resistant prostate cancer (mCRPC) patients. Tumor assessment and PSA values will be evaluated during the study as an additional point.

Official Title
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Phase I Open-label Single- and Multiple-ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ONC1-0013B in Patients With Progressive Metastatic Castration-resistant Prostate Cancer (mCRPC)

Conditions
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Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Intervention / Treatment
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* Drug: ONC1-0013B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men aged 18 years and older. Histologically confirmed diagnosis of prostate cancer Castrate level of testosterone in blood serum < 1,7 nmol/l or < 50 ng/dl PSA level at screening > 2 ng/ml Progression of metastatic CRPC after the chemical castration with gonadotropin-releasing hormone (GnRH) analogue or after the chemical castration and subsequent chemotherapy. The patient's ECOG performance status of 0 - 2 Patients previously treated with docetaxel chemotherapy should have received 2 or less prior lines of chemotherapy for mCRPC The expected survival time of not less than 12 weeks Exclusion Criteria: Prior anticancer therapy: Treatment with chemotherapeutic agents or radiotherapy within 4 weeks prior to screening or preserved toxicities of ≥ II grade according to CTCAE scale, related to prior anticancer therapy (excluding alopecia) Prior antiandrogen therapy: flutamide within 4 weeks prior to screening or bicalutamide within 6 weeks prior to screening Exposure to bisphosphonates is allowed only if the treatment started prior to screening Clinically significant cardiovascular system diseases: Clinically significant central nervous system diseases: History of other significant concomitant diseases which, in the Investigator's opinion, may cause a disease recurrence (i.e. uncontrolled diabetes mellitus) Prior or concomitant therapy: Exposure to drugs which may cause a convulsive state within 4 weeks prior to screening Exposure to treatment with characteristics of CYP3A4 or CYP2D6 inhibitors within 4 weeks prior to screening Exposure to treatment relating to the Class I risk of QT-interval prolongation; exposure to treatment relating to the Class II risk of QT-interval prolongation is allowed if the patient have received not less than 5 half-life periods of flat-dosed treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ONC1-0013B 40 mg<br>ONC1-0013B 40 mg per os daily | Drug: ONC1-0013B<br>* ONC1-0013B per os daily<br>|
| Experimental: ONC1-0013B 80 mg<br>ONC1-0013B 80 mg per os daily | Drug: ONC1-0013B<br>* ONC1-0013B per os daily<br>|
| Experimental: ONC1-0013B 160 mg<br>ONC1-0013B 160 mg per os daily | Drug: ONC1-0013B<br>* ONC1-0013B per os daily<br>|
| Experimental: ONC1-0013B 320 mg<br>ONC1-0013B 320 mg per os daily | Drug: ONC1-0013B<br>* ONC1-0013B per os daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT within 4 weeks of ONC1-0013B administration (safety and tolerability) | Incidence rate and severity of adverse events, changes in laboratory tests | 4 weeks and during the study up to 76 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | PK analysis of ONC1-0013B after single and multiple dosage | 28 days | 
| Area under the plasma concentration versus time curve (AUC) | PK analysis of ONC1-0013B after single and multiple dosage | 28 days | 
| Elimination half-life (T1/2) | PK analysis of ONC1-0013B after single and multiple dosage | 28 days | 
| Time-to-peak concentration (tmax) | PK analysis of ONC1-0013B after single and multiple dosage | 28 days | 
| Steady-State Concentration (Css) | PK analysis of ONC1-0013B after single and multiple dosage | 28 days | 
| Tumor response | RECIST 1.1 criteria and the change of the PSA level | 12 weeks and during the study up to 76 weeks |