Purpose

This is a Phase I multi-center, open-label, study of DST-2970 to determine the MTD, overall safety/tolerability, PK/pharmacodynamic parameters, and efficacy in prostate cancer patients.The study will include a dose escalation phase followed by a dose expansion phase. Each cohort will consist of a "run-in" period to assess pharmacokinetic trough, as well as C1hour, C2hour, and C3hour levels of standard of care abiraterone acetate, followed by a minimum of an 80-hour washout (treatment delay), then initiation of treatment with DST-2970. The patient population that will be evaluated in this study include patients with castration sensitive or castration resistant prostate cancer who experience a rising PSA, with or without radiographic progression, while taking abiraterone acetate. In this protocol, "initial PSA response to abiraterone" is defined as having a ≥ 30% drop in PSA levels (confirmed by a second PSA level one month later) during the first 6 months of treatment with abiraterone. These patients who subsequently experience a rise in PSA while on abiraterone are considered as having "acquired resistance" to abiraterone in the context of this protocol. Patients not meeting the definition of having an "initial PSA response to abiraterone" are considered as having "primary resistance" to abiraterone in the context of the protocol. In the dose escalation phase, all patients with a rising PSA can be enrolled, whether they had an "initial PSA response to abiraterone" or never responded to abiraterone. Two expansion cohorts will be opened. One expansion cohort will evaluate patients who did achieve an "initial PSA response to abiraterone" within the first 6 months of treatment as defined above, but subsequently progressed by PSA with or without radiographic progression. A second expansion cohort will evaluate patients who did not achieve an "initial PSA response to abiraterone" as defined above but have PSA progression with or without radiographic progression. The rationale of the study is to determine if the better bioavailability of DST-2970 will overcome resistance to abiraterone acetate experienced in these two clinical settings. In all cohorts, treatment will continue until progressive disease, unacceptable toxicity, investigator and/or sponsor decision, intercurrent illness or patient withdrawal of consent. Patients will be monitored regularly with physical examination and laboratory tests.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Male patients who have histologically or cytologically confirmed adenocarcinoma of the prostate (castrate sensitive or castrate resistant) and are taking abiraterone acetate as a single agent or in combination with Androgen Deprivation Therapy (ADT)
  2. Patients have prostate-specific antigen (PSA) progression (increasing PSA confirmed by sequence of rising values at a minimum of 1-week intervals, 1.0 ng/mL minimum starting value) or radiographic progression
  3. For Expansion Cohorts:
  4. Expansion Cohort 1: History of achieved an "initial PSA response to abiraterone"
  5. Expansion Cohort 2: History of not having achieved an "initial PSA response to abiraterone"
  6. Age ≥ 18 years.
  7. ECOG Performance Status 0 or 1
  8. Patients must have the following laboratory values:
  9. ANC > 1500/μL
  10. Platelet count >100,000/μL
  11. Hemoglobin > 9 g/dL
  12. Bilirubin < 1.5 x upper limits of normal
  13. ALT and AST < 2.5x upper limits of normal
  14. Creatinine ≤ 1.5 × upper limits of normal
  15. Albumin > 2.8 g/dL.
  16. Patient consent has been obtained according to local Institutional Review Board for acquisition of research specimens
  17. Patient is accessible and compliant for follow-up
  18. Patients with female partners of childbearing potential must agree to use barrier contraception (male condom) during the treatment period and for at least 30 days after the last dose
  19. Patient has a life expectancy of greater than 12 weeks

Exclusion Criteria

  1. Previous treatment with chemotherapy in the castrate resistant setting
  2. Positive for the ARV7 variant
  3. History of failure after previous treatment with androgen receptor blockers (e.g., enzalutamide, flutamide, apalutamide)
  4. Patients who had received previous therapy with ketoconazole for prostate cancer, lasting more than 7 days
  5. Have not recovered from adverse events (must be Grade ≤1) due to agents administered more than 4 weeks earlier
  6. Known hypersensitivity to any study drug component, or experienced grade 3 toxicity or higher with abiraterone acetate
  7. Concomitant use of strong CYP3A4 inducers unless these can be discontinued before enrollment into the study
  8. Concomitant use of strong CYP2D6 and CYP2C8 inducers unless these can be discontinued during the study
  9. Any concomitant condition that in the opinion of the investigator could compromise the objectives of this study and the patient's compliance
  10. Current malignancies of another type, with the exception of adequately treated in situ basal cell skin cancer or other malignancies with no evidence of disease for 2 years or more
  11. Known active HIV, HBV or HCV infection. Patients with a history of hepatitis B or C are allowed if HBV DNA or Hep C RNA are undetectable
  12. Documented or known serious bleeding disorder
  13. Clinically evident CNS metastases or leptomeningeal disease not controlled by prior surgery or radiotherapy; history of seizure disorder not controlled by anti-seizure medication at the time of enrollment. Patients with primary CNS malignancies are excluded
  14. Patients with a significant cardiovascular disease or condition, including:
  15. Myocardial infarction within 6 months of study entry
  16. NYHA Class III or IV heart failure, or known LVEF <50%
  17. Uncontrolled dysrhythmias or poorly controlled angina
  18. History of serious ventricular arrhythmia (VT or VF, ≥ 3 beats in a row) and/or risk factors (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
  19. Hypertension Grade 3 or higher. Patients with adequately treated hypertension are allowed

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
N/A
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Prostate Cancer
  • Drug: Abiraterone Acetate
    Abiraterone Acetate 1000mg will be administered orally once daily
  • Drug: Prednisone 5Mg Tab
    Prednisone 5mg will be administered orally twice daily with Abiraterone Acetate 1000mg Prednisone 5mg will be administered orally twice daily with DST-2970 for 28 days after dosing of Abiraterone Acetate is stopped
  • Drug: DST-2970 (Abiraterone)
    DST-2970 will be administered orally twice daily for 28 days (for every cycle) after dosing of Abiraterone Acetate is stopped

Recruiting Locations

Mays Cancer Center
San Antonio, Texas 78229
Contact:
Jennifer Moseley
210-450-1799
moseleyj@uthscsa.edu

More Details

Status
Recruiting
Sponsor
DisperSol Technologies, LLC

Study Contact

Cameron Wright, MS
602-358-8341
cwright@td2inc.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.