Clinical Trials /

Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CC-94676 in Subjects With Metastatic Castration-Resistant Prostate Cancer

NCT04428788

Description:

This is a first in human study to assess the safety, tolerability, PK, PD and preliminary efficacy of CC-94676 in men with progressive metastatic castration-resistant prostate cancer.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CC-94676 in Subjects With Metastatic Castration-Resistant Prostate Cancer
  • Official Title: A Phase 1, Multi-center, Open-label, Dose Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cc-94676 in Subjects With Metastatic Castration-resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: CC-94676-PCA-001
  • SECONDARY ID: U1111-1251-9174
  • NCT ID: NCT04428788

Conditions

  • Prostatic Neoplasms

Interventions

DrugSynonymsArms
CC-94676Administration of CC-94676

Purpose

This is a first in human study to assess the safety, tolerability, PK, PD and preliminary efficacy of CC-94676 in men with progressive metastatic castration-resistant prostate cancer.

Detailed Description

      Study CC-94676-PCA-001 is a first-in-human dose finding study to determine the safety,
      tolerability, PK, PD, and preliminary efficacy of CC-94676 in subjects with mCRPC who have
      progressed on ADT and at least one prior secondary hormonal therapy approved for CRPC (eg,
      abiraterone, enzalutamide, apalutamide, or darolutamide). The dose escalation will evaluate
      the safety and tolerability of escalating doses of CC-94676 in mCRCP subjects to determine
      the MTD of CC-94676. The dose expansion will further evaluate the safety and preliminary
      efficacy of CC-94676 administered at or below MTD in subjects with mCRPC.
    

Trial Arms

NameTypeDescriptionInterventions
Administration of CC-94676ExperimentalEscalating doses of CC-94676 administered orally (tablets) once daily.
  • CC-94676

Eligibility Criteria

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study:

          1. Subject is a male ≥ 18 years of age at the time of signing the informed consent form
             (ICF).

          2. Subjects must have histologically or cytologically confirmed adenocarcinoma of the
             prostate.

          3. Subjects must have documented progressive metastatic castration-resistant prostate
             cancer (CRPC).

          4. Subjects must have progressed on androgen deprivation therapy (ADT) and at least one
             prior secondary hormonal therapy approved for CRPC (eg, abiraterone, enzalutamide,
             apalutamide, or darolutamide).

          5. Subjects must have serum testosterone ≤ 50 ng/dL. Subjects must continue primary
             androgen deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue
             (agonist or antagonist) if they have not undergone bilateral orchiectomy.

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from enrollment:

          1. Subject has confirmed or suspected small cell carcinoma of the prostate/neuroendocrine
             prostate cancer.

          2. Subject has known symptomatic brain or epidural central nervous system (CNS) or spinal
             metastases requiring steroids (above physiologic replacement doses) or radiation.

          3. Subject had systemic anticancer therapy or investigational treatments within 4 weeks
             (except treatments to maintain castrate status) or ≤ 5 half-lives prior to the first
             dose of CC-94676, whichever is shorter.

          4. Subject had palliative radiation, strontium-89, or radium-223 ≤ 4 weeks prior to the
             first dose of CC-94676. Palliative radiation for the alleviation of pain due to bone
             metastasis will be allowed during the study, as long as this is not a sign of
             clinically significant disease progression.

          5. Subject has any significant medical condition, such as uncontrolled infection,
             laboratory abnormality, or psychiatric illness that would prevent the subject from
             participating in the study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:From the time of consent at screening until 28 days after the subject discontinues study treatment.
Safety Issue:
Description:Type, frequency, seriousness, severity and relationship of AEs to CC-94676.

Secondary Outcome Measures

Measure:Confirmed Prostate Specific Antigen (PSA) decline of ≥ 50% from baseline (PSA50)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:is defined as a ≥ 50% reduction in PSA from baseline to the lowest postbaseline PSA value and required confirmation by a consecutive assessment at least 3 weeks later (PSA50).
Measure:Objective soft tissue response
Time Frame:Up to approximately 4 years
Safety Issue:
Description:The proportion of subjects who achieve a best response of partial response or better (PR or CR) per Prostate Cancer Clinical Trials Working Group 3 (PCWG3).
Measure:Duration of response (DOR)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:is defined as the time from the earliest date of documented soft tissue response (PR or CR based on PCWG3) to the first documented soft tissue disease progression or death, whichever occurs first.
Measure:Proportion of subjects alive and not progressed at 6 months
Time Frame:Up to 6 months after treatment is discontinued
Safety Issue:
Description:The proportion of subjects alive and who have not progressed at 6 months follow-up with progression defined by PCWG3.
Measure:PSA Progression Free Survival (PFS)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:PSA PFS will be calculated for all treated subjects as, after a decline from baseline, the time from the first dose of CC-94676 to the first PSA increase that is ≥ 25% and a ≥ 2 ng/mL above the nadir, and which is confirmed by a second value ≥ 3 weeks later. When there is no decline from baseline, then PSA progression is ≥ 25% increase and a ≥ 2 ng/mL increase from baseline beyond 12 weeks.
Measure:Radiographic progression free survival (rPFS)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:The time from the first dose of CC-94676 to the first objective evidence of radiographic progression or death from any cause, whichever occurs first.
Measure:Overall survival (OS)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:OS is the time from the first dose of CC-94676 to death from any cause.
Measure:Overall Survival (OS) rate
Time Frame:Up to approximately 4 years
Safety Issue:
Description:will be summarized using the Kaplan-Meier method for the treated population.
Measure:Pharmacokinetics - AUC
Time Frame:Up to 35 days
Safety Issue:
Description:Area under the plasma concentration time curve
Measure:Pharmacokinetics - Cmax
Time Frame:Up to 35 days
Safety Issue:
Description:Maximum plasma concentration
Measure:Pharmacokinetics - Tmax
Time Frame:Up to 35 days
Safety Issue:
Description:Time to Cmax
Measure:Pharmacokinetics - t1/2
Time Frame:Up to 35 days
Safety Issue:
Description:Terminal half-life
Measure:Pharmacokinetics - CL/F
Time Frame:Up to 35 days
Safety Issue:
Description:Apparent total clearance of the drug from plasma after oral administration
Measure:Pharmacokinetics - Vz/F
Time Frame:Up to 35 days
Safety Issue:
Description:Apparent volume of distribution during terminal phase after oral administration

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Celgene

Trial Keywords

  • Prostate Cancer
  • CC-94676
  • Castration-resistant prostate cancer
  • Adenocarcinoma of the prostate
  • Prostatic Neoplasms Castration-Resistant
  • Neoplasms

Last Updated

August 3, 2020