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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04631601




Registration number
NCT04631601
Ethics application status
Date submitted
13/11/2020
Date registered
17/11/2020

Titles & IDs
Public title
Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)
Scientific title
A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)
Secondary ID [1] 0 0
2020-001305-23
Secondary ID [2] 0 0
20190505
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Castration-resistant Prostate Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Acapatamab
Treatment: Drugs - Enzalutamide
Treatment: Drugs - Abiraterone
Treatment: Drugs - AMG 404

Experimental: Acapatamab and Enzalutamide: Dose Exploration - The dose-exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with enzalutamide.

Experimental: Acapatamab and Enzalutamide: Dose Expansion - Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with enzalutamide.

Experimental: Acapatamab and Abiraterone: Dose Exploration - The dose exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with abiraterone.

Experimental: Acapatamab and Abiraterone: Dose Expansion - Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with abiraterone.

Experimental: Acapatamab and AMG 404: Dose Exploration - The dose-exploration part of the study will estimate the MTD/RP2D of Acapatamab in combination with AMG 404.

Experimental: Acapatamab and AMG 404: Dose Expansion - Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with AMG 404.

Active comparator: AMG 404 Monotherapy - AMG 404 monotherapy is being conducted to evaluate the preliminary anti-tumor activity of PD-1 inhibition in the mCRPC population.

Experimental: Acapatamab and Enzalutamide: Dose Expansion Asia Cohort - Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with enzalutamide for subjects in Asia.

Experimental: Acapatamab and Abiraterone: Dose Expansion Asia Cohort - Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with abiraterone for subjects in Asia.

Experimental: Acapatamab and AMG 404: Dose Expansion Asia Cohort - Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with AMG 404 for subjects in Asia.

Experimental: Acapatamab Monotherapy - Acapatamab monotherapy is being conducted to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of Acapatamab in subjects with mCRPC.


Treatment: Drugs: Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.

Treatment: Drugs: Enzalutamide
Enzalutamide will be administered orally.

Treatment: Drugs: Abiraterone
Abiraterone will be administered orally.

Treatment: Drugs: AMG 404
AMG 404 will be administered as an intravenous (IV) infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose exploration only: Number of participants who experience dose limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to 3 years
Primary outcome [2] 0 0
Number of participants who experience one or more treatment-emergent adverse events (TEAEs)
Timepoint [2] 0 0
Up to 3 years
Primary outcome [3] 0 0
Number of participants who experience one or more treatment-related adverse events
Timepoint [3] 0 0
Up to 3 years
Primary outcome [4] 0 0
Number of participants who experience a clinically significant change in vital signs
Timepoint [4] 0 0
Up to 3 years
Primary outcome [5] 0 0
Number of participants who experience a clinically significant change in clinical laboratory tests
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [1] 0 0
Objective response rate per response evaluation criteria in solid tumors (RECIST) 1.1 with prostate cancer working group 3 (PCWG3) modifications
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Number of participants who experience circulating tumor cell (CTC) response
Timepoint [2] 0 0
Up to 3 years
Secondary outcome [3] 0 0
Number of participants who experience prostate-specific antigen (PSA) response rate
Timepoint [3] 0 0
Up to 3 years
Secondary outcome [4] 0 0
Duration of response
Timepoint [4] 0 0
Up to 3 years
Secondary outcome [5] 0 0
Overall survival (OS)
Timepoint [5] 0 0
Up to 3 years
Secondary outcome [6] 0 0
Progression-free survival
Timepoint [6] 0 0
Up to 3 years
Secondary outcome [7] 0 0
Time to progression
Timepoint [7] 0 0
Up to 3 years
Secondary outcome [8] 0 0
Time to subsequent therapy
Timepoint [8] 0 0
Up to 3 years
Secondary outcome [9] 0 0
Maximum plasma concentration (Cmax)
Timepoint [9] 0 0
Up to 3 years
Secondary outcome [10] 0 0
Minimum plasma concentration (Cmin)
Timepoint [10] 0 0
Up to 3 years
Secondary outcome [11] 0 0
Area under the concentration-time curve (AUC)
Timepoint [11] 0 0
Up to 3 years
Secondary outcome [12] 0 0
Accumulation ratio based on area under the concentration-time curve (AUC)
Timepoint [12] 0 0
Up to 3 years
Secondary outcome [13] 0 0
Half-life (t1/2)
Timepoint [13] 0 0
Up to 3 years
Secondary outcome [14] 0 0
Change from baseline in prostate-specific membrane antigen (PSMA)-positive tumor burden assessed using gallium (GA) 68-labelled PSMA-11 positron emission tomography/computed tomography (PET/CT)
Timepoint [14] 0 0
Baseline up to 3 years
Secondary outcome [15] 0 0
Change from baseline in prostate-specific membrane antigen (PSMA)-negative disease burden assessed using 18F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT)
Timepoint [15] 0 0
Baseline to 3 years
Secondary outcome [16] 0 0
Time to symptomatic skeletal events
Timepoint [16] 0 0
Up to 3 years
Secondary outcome [17] 0 0
Concentration of alkaline phosphatase
Timepoint [17] 0 0
Up to 3 years
Secondary outcome [18] 0 0
Concentration of lactate dehydrogenase (LDH)
Timepoint [18] 0 0
Up to 3 years
Secondary outcome [19] 0 0
Concentration of hemoglobin
Timepoint [19] 0 0
Up to 3 years
Secondary outcome [20] 0 0
Neutrophil-to-lymphocyte ratio
Timepoint [20] 0 0
Up to 3 years
Secondary outcome [21] 0 0
Concentration of N-telopeptide in the urine
Timepoint [21] 0 0
Up to 3 years

Eligibility
Key inclusion criteria
All parts



* = 18 years of age (or legal adult age within country)
* Subject has provided informed consent prior to initiation of any study-specific activities/procedures
* Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate
* Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist (testosterone = 50 ng/dL (or 1.7 nmol/L))
Minimum age
18 Years
Maximum age
99 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Central nervous system (CNS) metastases or leptomeningeal disease
* History or presence of clinically relevant CNS pathology
* Confirmed history or current autoimmune disease or other diseases requiring permanent immunosuppressive therapy
* Myocardial infarction, uncontrolled hypertension, unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months
* Prior treatment with a taxane for mCRPC
* Major surgery and/or Radiation within 4 weeks
* History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless agreed upon with medical monitor and meeting the following criteria:

* Negative test for SARS-CoV-2 RNA by real time polymerase chain reaction (RT-PCR) within 72 hours of first dose of Acapatamab (or AMG 404 in Part 3)
* No acute symptoms of COVID-19 disease within 10 days prior to first dose of Acapatamab (or AMG 404 in Part 3) (counted from day of positive test for asymptomatic subjects)

Prior/Concurrent Clinical Study Experience

* Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded with the exception of investigational scans.

Subprotocol A only:

Inclusion criteria

• Subjects planning to receive enzalutamide for the first time for mCRPC

Exclusion criteria

* Use of strong CYP2C8 inhibitors or strong CYP3A4 inducers
* Use of narrow therapeutic index drugs that are substrates of CYP3A4, CYP2C9 or CYP2C19

Subprotocol B only:

Inclusion criteria

* Subjects planning to receive abiraterone for the first time for mCRPC Exclusion criteria
* Baseline moderate and severe hepatic impairment (Child-Pugh Class B and C)
* Presence of uncontrolled hypertension, hypokalemia, or fluid retention
* History or presence of adrenocortical insufficiency
* Use of concomitant medications that are sensitive substrates for CYP2D6 with a narrow therapeutic index
* Use of strong CYP3A4 inducers

Subprotocol C only:

Inclusion criteria

* Subjects who are refractory to a novel antiandrogen therapy. Subjects must be ineligible for or refuse taxane therapy.
* Evidence of progressive disease, defined as 1 or more PCWG3 criteria: PSA level >/=1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart, nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications, and/or appearance of 2 or more new lesions in bone scan Exclusion criteria
* History or evidence of interstitial lung disease or active, non-infectious pneumonitis
* Subjects on a prior PD-1 or PD-L1 inhibitor who experienced a grade 3 or higher immune-related adverse event prior to first day of dose

Subprotocol D only:

Inclusion criteria

* Subjects may have had novel hormonal therapies (NHT; eg, abiraterone, enzalutamide, apalutamide, or darolutamide) for prostate cancer, but no more than 1 NHT for metastatic prostate cancer
* Ineligible for or refuse taxane therapy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/01/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/10/2023
Sample size
Target
Accrual to date
Final
65
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St Vincents Hospital Sydney - Darlinghurst
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Denmark
State/province [6] 0 0
Kobenhavn O
Country [7] 0 0
Spain
State/province [7] 0 0
Navarra
Country [8] 0 0
Sweden
State/province [8] 0 0
Lund
Country [9] 0 0
Sweden
State/province [9] 0 0
Stockholm
Country [10] 0 0
Sweden
State/province [10] 0 0
Uppsala
Country [11] 0 0
United Kingdom
State/province [11] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://www.amgen.com/datasharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04631601