History of Changes for Study: NCT04428788

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

A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.

Study Record Versions

Version	Submitted Date	Changes
1	June 10, 2020	None (earliest Version on record)
2	July 31, 2020	Recruitment Status, Study Status, Contacts/Locations and Study Identification
3	August 3, 2020	Study Status and Contacts/Locations
4	January 5, 2021	Study Status and Contacts/Locations
5	January 12, 2021	Contacts/Locations and Study Status
6	May 5, 2021	Study Status, Contacts/Locations, Eligibility and Study Design
7	February 8, 2022	Contacts/Locations, Outcome Measures, Study Status, Eligibility, Arms and Interventions, Study Design, Study Description and Study Identification
8	April 29, 2022	Study Status, References, Contacts/Locations and Study Identification
9	May 24, 2022	Study Status, References, Contacts/Locations and Eligibility
10	May 31, 2022	Contacts/Locations and Study Status
11	July 27, 2022	Study Status, Contacts/Locations, Eligibility and Study Design
12	August 17, 2022	Contacts/Locations and Study Status
13	October 7, 2022	Contacts/Locations and Study Status
14	November 3, 2022	Contacts/Locations and Study Status
15	December 1, 2022	Contacts/Locations and Study Status
16	December 5, 2022	Contacts/Locations and Study Status
17	February 24, 2023	Contacts/Locations and Study Status
18	April 20, 2023	Contacts/Locations and Study Status
19	May 15, 2023	Study Status and Contacts/Locations
20	June 5, 2023	Contacts/Locations and Study Status
21	July 25, 2023	Arms and Interventions, Study Status, Contacts/Locations, Outcome Measures and Study Design
22	November 7, 2023	Contacts/Locations, Arms and Interventions, Study Status and Study Design
23	March 29, 2024	Contacts/Locations, References and Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	CC-94676-PCA-001
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
Secondary IDs:	U1111-1251-9174 [WHO]

Study Status


Record Verification:	June 2020
Overall Status:	Not yet recruiting
Study Start:	June 19, 2020
Primary Completion:	April 27, 2024 [Anticipated]
Study Completion:	April 27, 2024 [Anticipated]

First Submitted:	May 29, 2020
First Submitted that Met QC Criteria:	June 10, 2020
First Posted:	June 11, 2020 [Actual]

Last Update Submitted that Met QC Criteria:	June 10, 2020
Last Update Posted:	June 11, 2020 [Actual]

Sponsor/Collaborators


Sponsor:	Celgene
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	No

Study Description

Brief Summary:

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.

Conditions


Conditions:	Prostatic Neoplasms
Keywords:	Prostate Cancer CC-94676 Castration-resistant prostate cancer Adenocarcinoma of the prostate Prostatic Neoplasms Castration-Resistant Neoplasms

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1
Interventional Study Model:	Single Group Assignment
Number of Arms:	1
Masking:	None (Open Label)
Allocation:	N/A
Enrollment:	40 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Administration of CC-94676 Escalating doses of CC-94676 administered orally (tablets) once daily.	Drug: CC-94676 CC-94676

Outcome Measures


Primary Outcome Measures:
1.	Adverse Events (AEs) [ Time Frame: From the time of consent at screening until 28 days after the subject discontinues study treatment. ] Type, frequency, seriousness, severity and relationship of AEs to CC-94676.
2.	Dose-limiting Toxicities (DLTs) [ Time Frame: Up to 35 days ] Number of subjects with a DLT.
3.	Non-Tolerated Dose (NTD) [ Time Frame: Up to 35 days ] The dose of CC-94676 associated with unacceptable safety and tolerability.
4.	Maximum Tolerated Dose (MTD) [ Time Frame: Up to 35 days ] The highest dose of CC-94676 associated with acceptable safety and tolerability.
Secondary Outcome Measures:
1.	Confirmed Prostate Specific Antigen (PSA) decline of ≥ 50% from baseline (PSA50) [ Time Frame: Up to approximately 4 years ] 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).
2.	Objective soft tissue response [ Time Frame: Up to approximately 4 years ] 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).
3.	Duration of response (DOR) [ Time Frame: Up to approximately 4 years ] 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.
4.	Proportion of subjects alive and not progressed at 6 months [ Time Frame: Up to 6 months after treatment is discontinued ] The proportion of subjects alive and who have not progressed at 6 months follow-up with progression defined by PCWG3.
5.	PSA Progression Free Survival (PFS) [ Time Frame: Up to approximately 4 years ] 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.
6.	Radiographic progression free survival (rPFS) [ Time Frame: Up to approximately 4 years ] 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.
7.	Overall survival (OS) [ Time Frame: Up to approximately 4 years ] OS is the time from the first dose of CC-94676 to death from any cause.
8.	Overall Survival (OS) rate [ Time Frame: Up to approximately 4 years ] will be summarized using the Kaplan-Meier method for the treated population.
9.	Pharmacokinetics - AUC [ Time Frame: Up to 35 days ] Area under the plasma concentration time curve
10.	Pharmacokinetics - Cmax [ Time Frame: Up to 35 days ] Maximum plasma concentration
11.	Pharmacokinetics - Tmax [ Time Frame: Up to 35 days ] Time to Cmax
12.	Pharmacokinetics - t1/2 [ Time Frame: Up to 35 days ] Terminal half-life
13.	Pharmacokinetics - CL/F [ Time Frame: Up to 35 days ] Apparent total clearance of the drug from plasma after oral administration
14.	Pharmacokinetics - Vz/F [ Time Frame: Up to 35 days ] Apparent volume of distribution during terminal phase after oral administration

Eligibility


Minimum Age:	18 Years
Maximum Age:
Sex:	Male
Gender Based:	Yes
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Subjects must satisfy the following criteria to be enrolled in the study: Subject is a male ≥ 18 years of age at the time of signing the informed consent form (ICF). Subjects must have histologically or cytologically confirmed adenocarcinoma of the prostate. Subjects must have documented progressive metastatic castration-resistant prostate cancer (CRPC). 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). 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: Subject has confirmed or suspected small cell carcinoma of the prostate/neuroendocrine prostate cancer. Subject has known symptomatic brain or epidural central nervous system (CNS) or spinal metastases requiring steroids (above physiologic replacement doses) or radiation. 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. 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. 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.

Contacts/Locations


Central Contact Person:	Associate Director Clinical Trial Disclosure Telephone: 1-888-260-1599 Email: clinicaltrialdisclosure@celgene.com
Study Officials:	Marie Nguyen, MD Study Director Celgene
Locations:

IPDSharing


Plan to Share IPD:	Yes Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
	Supporting Information: Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) Analytic Code
	Time Frame: See Plan Description
	Access Criteria: See Plan Description
	URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

References


Citations:
Links:
Available IPD/Information: