Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)

Metastatic Castration-resistant Prostate Cancer Clinical Trial

Official title:

A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04631601
• Other study ID #: 20190505
• Secondary ID: 2020-001305-23
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: January 15, 2021
• Est. completion date: October 23, 2023

Study information

• Verified date: November 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a master protocol designed to evaluate the safety and efficacy of investigational therapies in participants with metastatic castration-resistant prostate cancer (mCRPC).

Description:

This is a master protocol designed to evaluate the safety, tolerability, and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and efficacy of Acapatamab, in combination with enzalutamide, abiraterone, or the PD1 inhibitor AMG 404, AMG 404 monotherapy, as well as Acapatamab monotherapy, in participants with metastatic castration-resistant prostate cancer (mCRPC).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 65
• Est. completion date: October 23, 2023
• Est. primary completion date: October 23, 2023
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 99 Years

Eligibility

All parts

Inclusion Criteria:

• = 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))

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

Related Conditions & MeSH terms

• Metastatic Castration-resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Acapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
• Enzalutamide
Enzalutamide will be administered orally.
• Abiraterone
Abiraterone will be administered orally.
• AMG 404
AMG 404 will be administered as an intravenous (IV) infusion.

Locations

Country	Name	City	State
Australia	St Vincents Hospital Sydney	Darlinghurst	New South Wales
Denmark	Rigshospitalet	Kobenhavn O
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Sweden	Skanes universitetssjukhus	Lund
Sweden	Karolinska Universitetssjukhuset Solna	Stockholm
Sweden	Akademiska sjukhuset	Uppsala
United Kingdom	Royal Marsden Hospital	Sutton
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Chicago	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of California at Irvine Medical Center	Orange	California
United States	University of California San Francisco Mission Bay Campus	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  Denmark,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose exploration only: Number of participants who experience dose limiting toxicities (DLTs)	The analysis of all endpoints, unless noted otherwise, will be conducted on the Safety Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of Acapatamab. The analysis of dose-limiting toxicity (DLT) will be conducted on the DLT Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of Acapatamab with an evaluable DLT endpoint. If a single subject experiences more than 1 DLT it will be counted as 1.; The DLT endpoint is evaluable if either: 1) the subject experiences a DLT; or 2) the subject does not experience a DLT after receiving all planned doses within the 28-day DLT window in cycle 1.	Up to 3 years
Primary	Number of participants who experience one or more treatment-emergent adverse events (TEAEs)		Up to 3 years
Primary	Number of participants who experience one or more treatment-related adverse events		Up to 3 years
Primary	Number of participants who experience a clinically significant change in vital signs		Up to 3 years
Primary	Number of participants who experience a clinically significant change in clinical laboratory tests		Up to 3 years
Secondary	Objective response rate per response evaluation criteria in solid tumors (RECIST) 1.1 with prostate cancer working group 3 (PCWG3) modifications		Up to 3 years
Secondary	Number of participants who experience circulating tumor cell (CTC) response		Up to 3 years
Secondary	Number of participants who experience prostate-specific antigen (PSA) response rate		Up to 3 years
Secondary	Duration of response		Up to 3 years
Secondary	Overall survival (OS)		Up to 3 years
Secondary	Progression-free survival		Up to 3 years
Secondary	Time to progression		Up to 3 years
Secondary	Time to subsequent therapy		Up to 3 years
Secondary	Maximum plasma concentration (Cmax)		Up to 3 years
Secondary	Minimum plasma concentration (Cmin)		Up to 3 years
Secondary	Area under the concentration-time curve (AUC)		Up to 3 years
Secondary	Accumulation ratio based on area under the concentration-time curve (AUC)		Up to 3 years
Secondary	Half-life (t1/2)		Up to 3 years
Secondary	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)		Baseline up to 3 years
Secondary	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)		Baseline to 3 years
Secondary	Time to symptomatic skeletal events		Up to 3 years
Secondary	Concentration of alkaline phosphatase		Up to 3 years
Secondary	Concentration of lactate dehydrogenase (LDH)		Up to 3 years
Secondary	Concentration of hemoglobin		Up to 3 years
Secondary	Neutrophil-to-lymphocyte ratio		Up to 3 years
Secondary	Concentration of N-telopeptide in the urine		Up to 3 years

External Links

•   AmgenTrials clinical trials website