Clinical trial NCT03074032: Safety, Tolerability and Pharmacokinetics of ONC1-0013B in Patients With Progressive Metastatic Castration-resistant Prostate Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Lead sponsor: Avionco LLC
Sponsor class: INDUSTRY
First posted: 2017-03-08
Enrollment: 17
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Single Group Assignment
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: DLT within 4 weeks of ONC1-0013B administration (safety and tolerability)
timeFrame: 4 weeks and during the study up to 76 weeks
Secondary outcomes:
measure: Peak Plasma Concentration (Cmax)
timeFrame: 28 days
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 28 days
measure: Elimination half-life (T1/2)
timeFrame: 28 days
measure: Time-to-peak concentration (tmax)
timeFrame: 28 days
measure: Steady-State Concentration (Css)
timeFrame: 28 days
measure: Tumor response
timeFrame: 12 weeks and during the study up to 76 weeks
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: 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)
city: Obninsk
country: Russian Federation
facility: Medical Radiological Research Center n.a. A.F. Tsyb (branch of FSBI NMRRC of the Ministry of Health of the Russian Federation)
Study officials:
References: