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

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)

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Castration-Resistant Prostate Cancer (mCRPC)
• Intervention / Treatment: Drug: ONC1-0013B

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 105426
    • 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)
  • Obninsk, Russian Federation, 249036
    • Medical Radiological Research Center n.a. A.F. Tsyb (branch of FSBI NMRRC of the Ministry of Health of the Russian Federation)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ONC1-0013B 40 mg; ONC1-0013B 40 mg per os daily	Drug: ONC1-0013B; ONC1-0013B per os daily
Experimental: ONC1-0013B 80 mg; ONC1-0013B 80 mg per os daily	Drug: ONC1-0013B; ONC1-0013B per os daily
Experimental: ONC1-0013B 160 mg; ONC1-0013B 160 mg per os daily	Drug: ONC1-0013B; ONC1-0013B per os daily
Experimental: ONC1-0013B 320 mg; ONC1-0013B 320 mg per os daily	Drug: ONC1-0013B; ONC1-0013B per os daily

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Avionco LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2014
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: March 3, 2017
• First Submitted That Met QC Criteria: March 3, 2017
• First Posted (Actual): March 8, 2017

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: July 8, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: ONC-ONC10013B-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No