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.
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
Interventions
Drug | Synonyms | Arms |
---|
CC-94676 | | Administration 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
Name | Type | Description | Interventions |
---|
Administration of CC-94676 | Experimental | Escalating doses of CC-94676 administered orally (tablets) once daily. | |
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.
6. Subjects must have discontinued bicalutamide ≥ 6 weeks prior to the first dose of
CC-94676. Subjects must have discontinued abiraterone, rucaparib, or olaparib ≥ 2
weeks prior to the first dose of CC-94676. Subjects must have discontinued
enzalutamide, flutamide, nilutamide, and other approved secondary hormonal therapy,
chemotherapy, immunotherapy, or investigational treatments (except treatments to
maintain castrate status) > 4 weeks prior to the first dose of CC-94676.
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 currently has symptomatic brain or epidural central nervous system (CNS) or
spinal metastases requiring steroids (above physiologic replacement doses) or
radiation.
3. 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.
4. 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
May 6, 2021