PK and Dose Escalation and Expansion Study of DST-2970

NCT04291664 | Terminated Phase 1 FDA Drug

• 1 other identifier: DST-2970-104
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (3)

• Maximum-tolerated dose (MTD)

  12-18 Months

• Recommended Phase II dose (RP2D)

  12-18 Months

• Dose-Limiting Toxicity

  12-18 Months

Secondary Outcomes (6)

• Pharmacokinetic analysis of trough, as well as C1hour, C2hour, and C3hour levels of abiraterone

  12-18 Months

• Change in Tumor Size

  12-18 Months

• Change in Prostate Specific Antigen (PSA)

  12-18 Months

• Duration of response (DoR)

  12-18 Months

• Type of response (e.g., CR, PR, SD)

  12-18 Months

Other Outcomes (1)

• Exploration of potential biomarkers

  12-18 Months

Study Arms (1)

Prostate Cancer

EXPERIMENTAL

Drug: Abiraterone Acetate; Drug: Prednisone 5Mg Tab; Drug: DST-2970 (Abiraterone)

Interventions

Abiraterone Acetate DRUG

Abiraterone Acetate 1000mg will be administered orally once daily

Prostate Cancer

Prednisone 5Mg Tab DRUG

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

Prostate Cancer

DST-2970 (Abiraterone) DRUG

DST-2970 will be administered orally twice daily for 28 days (for every cycle) after dosing of Abiraterone Acetate is stopped

Prostate Cancer

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male patients who have histologically or cytologically confirmed adenocarcinoma of the prostate (castrate sensitive or castrate resistant);
• During the dose escalation phase:
• Patients taking abiraterone acetate or enzalutamide as a single agent or in combination with Androgen Deprivation Therapy (ADT)
• During the expansion phase:
• Patients taking abiraterone acetate as a single agent or in combination with Androgen Deprivation Therapy (ADT).
• Patients who have prostate-specific antigen (PSA) progression;
• During the dose escalation phase: Increasing PSA confirmed by 3 rising values (1.0 ng/mL minimum starting value) with or without radiographic progression
• During the dose expansion phase: Increasing PSA confirmed by sequence of rising values at a minimum of 1-week intervals (1.0 ng/mL minimum starting value) with or without radiographic progression
• For the Expansion Cohorts
• Expansion Cohort 1: History of achieved an "initial PSA response to abiraterone" as defined in Section 3.1.
• Expansion Cohort 2: History of not having achieved an "initial PSA response to abiraterone as defined in Section 3.1.
• Age ≥ 18 years.
• ECOG Performance Status 0 or 1.
• Patients must have the following laboratory values:
• ANC \> 1500/µL

You may not qualify if:

• For the Expansion Cohorts:
• Previous treatment with chemotherapy in the castrate resistant setting
• Positive for the ARV7 variant
• History of failure after previous treatment with any androgen receptor blockers at any time (e.g., enzalutamide, apalutamide, darolutamide)
• a. Escalation Cohort: enzalutamide not excluded
• Patients who had received previous therapy with ketoconazole for prostate cancer, lasting more than 7 days.
• Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of \>450 msec in men
• Have not recovered from adverse events (must be Grade ≤1) due to agents administered more than 4 weeks earlier.
• Known hypersensitivity to any study drug component, or experienced grade 3 toxicity or higher with abiraterone acetate.
• Concomitant use of strong CYP3A4 inducers unless these can be discontinued before enrollment into the study.
• Concomitant use of sensitive CYP2D6 and CYP2C8 substrates unless these can be discontinued during the study (see Appendix 5)
• Any concomitant condition that in the opinion of the investigator could compromise the objectives of this study and the patient's compliance.
• 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.
• 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.
• Documented or known serious bleeding disorder.

Sponsors & Collaborators

• DisperSol Technologies, LLC: lead
• Translational Drug Development: collaborator

Study Sites (5)

University of Miami

Miami, Florida, 33136, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Prednisone; abiraterone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2019
• First Posted: March 2, 2020
• Study Start: January 31, 2020
• Primary Completion: January 27, 2023
• Study Completion: January 27, 2023
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)