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

Metastatic Castration-Resistant Prostate Cancer (mCRPC) Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03074032
• Other study ID #: ONC-ONC10013B-01
• Status: Completed
• Phase: Phase 1
• First received: March 3, 2017
• Last updated: July 8, 2017
• Start date: June 30, 2014
• Est. completion date: April 2017

Study information

• Verified date: July 2017
• Source: Avionco LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Metastatic Castration-Resistant Prostate Cancer (mCRPC)
• Prostatic Neoplasms

Intervention

Drug:
• ONC1-0013B
ONC1-0013B per os daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Avionco LLC

Country where clinical trial is conducted

Russian Federation, 

Outcome

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