Clinical Trials /

PK and Dose Escalation and Expansion Study of DST-2970

NCT04291664

Description:

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: PK and Dose Escalation and Expansion Study of DST-2970
  • Official Title: A Phase 1 PK and Dose Escalation and Expansion Study of DST-2970 in Patients With Prostate Cancer With Rising PSA on Treatment With Abiraterone Acetate

Clinical Trial IDs

  • ORG STUDY ID: DST-2970-104
  • NCT ID: NCT04291664

Conditions

  • Prostate Cancer

Interventions

DrugSynonymsArms
Abiraterone AcetateProstate Cancer
Prednisone 5Mg TabProstate Cancer
DST-2970 (Abiraterone)Prostate Cancer

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.

Trial Arms

NameTypeDescriptionInterventions
Prostate CancerExperimental
  • Abiraterone Acetate
  • Prednisone 5Mg Tab
  • DST-2970 (Abiraterone)

Eligibility Criteria

        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:

               1. Expansion Cohort 1: History of achieved an "initial PSA response to abiraterone"

               2. Expansion Cohort 2: History of not having achieved an "initial PSA response to
                  abiraterone"

          4. Age ≥ 18 years.

          5. ECOG Performance Status 0 or 1

          6. Patients must have the following laboratory values:

               1. ANC > 1500/μL

               2. Platelet count >100,000/μL

               3. Hemoglobin > 9 g/dL

               4. Bilirubin < 1.5 x upper limits of normal

               5. ALT and AST < 2.5x upper limits of normal

               6. Creatinine ≤ 1.5 × upper limits of normal

               7. Albumin > 2.8 g/dL.

          7. Patient consent has been obtained according to local Institutional Review Board for
             acquisition of research specimens

          8. Patient is accessible and compliant for follow-up

          9. 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

         10. 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:

               1. Myocardial infarction within 6 months of study entry

               2. NYHA Class III or IV heart failure, or known LVEF <50%

               3. Uncontrolled dysrhythmias or poorly controlled angina

               4. 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)

               5. Hypertension Grade 3 or higher. Patients with adequately treated hypertension are
                  allowed
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum-tolerated dose (MTD)
Time Frame:12-18 Months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Pharmacokinetic analysis of trough, as well as C1hour, C2hour, and C3hour levels of abiraterone
Time Frame:12-18 Months
Safety Issue:
Description:To evaluate the pharmacokinetic trough, as well as C1hour, C2hour, and C3hour levels of abiraterone following daily oral administration of DST-2970 to inform the dose selected for expansion in patients with prostate cancer
Measure:Change in Tumor Size
Time Frame:12-18 Months
Safety Issue:
Description:To measure the effectiveness of DST-2970 using CT scan results as measured by modified RECIST 1.1
Measure:Change in Prostate Specific Antigen (PSA)
Time Frame:12-18 Months
Safety Issue:
Description:To measure efficacy of DST-2970 using the blood marker PSA results
Measure:Duration of response (DoR)
Time Frame:12-18 Months
Safety Issue:
Description:To measure duration of response (DoR)
Measure:Type of response (e.g., CR, PR, SD)
Time Frame:12-18 Months
Safety Issue:
Description:To measure type of response (e.g., CR, PR, SD)
Measure:Time to Progression (rTTP) by PCWG3-modified RECIST v1.1
Time Frame:12-18 Months
Safety Issue:
Description:To measure Time to Progression (rTTP) by PCWG3-modified RECIST v1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:DisperSol Technologies, LLC

Last Updated

February 28, 2020