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

Phase 1
Completed
Conditions
Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Interventions
Registration Number
NCT03074032
Lead Sponsor
Avionco LLC
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
17
Inclusion Criteria
  1. Men aged 18 years and older.
  2. Histologically confirmed diagnosis of prostate cancer
  3. Castrate level of testosterone in blood serum < 1,7 nmol/l or < 50 ng/dl
  4. PSA level at screening > 2 ng/ml
  5. Progression of metastatic CRPC after the chemical castration with gonadotropin-releasing hormone (GnRH) analogue or after the chemical castration and subsequent chemotherapy.
  6. The patient's ECOG performance status of 0 - 2
  7. Patients previously treated with docetaxel chemotherapy should have received 2 or less prior lines of chemotherapy for mCRPC
  8. The expected survival time of not less than 12 weeks
Exclusion Criteria
  1. 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
  2. Clinically significant cardiovascular system diseases:

  3. Clinically significant central nervous system diseases:

  4. History of other significant concomitant diseases which, in the Investigator's opinion, may cause a disease recurrence (i.e. uncontrolled diabetes mellitus)

  5. 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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ONC1-0013B 160 mgONC1-0013BONC1-0013B 160 mg per os daily
ONC1-0013B 80 mgONC1-0013BONC1-0013B 80 mg per os daily
ONC1-0013B 320 mgONC1-0013BONC1-0013B 320 mg per os daily
ONC1-0013B 40 mgONC1-0013BONC1-0013B 40 mg per os daily
Primary Outcome Measures
NameTimeMethod
DLT within 4 weeks of ONC1-0013B administration (safety and tolerability)4 weeks and during the study up to 76 weeks

Incidence rate and severity of adverse events, changes in laboratory tests

Secondary Outcome Measures
NameTimeMethod
Area under the plasma concentration versus time curve (AUC)28 days

PK analysis of ONC1-0013B after single and multiple dosage

Elimination half-life (T1/2)28 days

PK analysis of ONC1-0013B after single and multiple dosage

Time-to-peak concentration (tmax)28 days

PK analysis of ONC1-0013B after single and multiple dosage

Tumor response12 weeks and during the study up to 76 weeks

RECIST 1.1 criteria and the change of the PSA level

Steady-State Concentration (Css)28 days

PK analysis of ONC1-0013B after single and multiple dosage

Peak Plasma Concentration (Cmax)28 days

PK analysis of ONC1-0013B after single and multiple dosage

Trial Locations

Locations (2)

Medical Radiological Research Center n.a. A.F. Tsyb (branch of FSBI NMRRC of the Ministry of Health of the Russian Federation)

🇷🇺

Obninsk, Russian Federation

Research Institute of Urology and Interventional Radiology n.a. N.A. Lopatkin (branch of FSBI NMRRC of the Ministry of Health of the Russian Federation)

🇷🇺

Moscow, Russian Federation

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