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

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ClinicalTrials.gov Identifier: NCT04631601
Recruitment Status : Recruiting
First Posted : November 17, 2020
Last Update Posted : July 8, 2021
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief 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).

Condition or disease Intervention/treatment Phase
Metastatic Castration-resistant Prostate Cancer Drug: AMG 160 Drug: Enzalutamide Drug: Abiraterone Drug: AMG 404 Phase 1

Detailed 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 AMG 160, in combination with enzalutamide, abiraterone, or the PD1 inhibitor AMG 404 as well as AMG 404 monotherapy, in participants with metastatic castration-resistant prostate cancer (mCRPC).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)
Actual Study Start Date : January 15, 2021
Estimated Primary Completion Date : April 30, 2025
Estimated Study Completion Date : May 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: AMG 160 and Enzalutamide: Dose Exploration
The dose-exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of AMG 160 in combination with enzalutamide.
Drug: AMG 160
AMG 160 will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: Enzalutamide
Enzalutamide will be administered orally.
Other Name: Androgen receptor inhibitor

Experimental: AMG 160 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 AMG 160 in combination with enzalutamide.
Drug: AMG 160
AMG 160 will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: Enzalutamide
Enzalutamide will be administered orally.
Other Name: Androgen receptor inhibitor

Experimental: AMG 160 and Abiraterone: Dose Exploration
The dose exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of AMG 160 in combination with abiraterone.
Drug: AMG 160
AMG 160 will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: Abiraterone
Abiraterone will be administered orally.
Other Name: Cytochrome P450 (CYP)17 inhibitor

Experimental: AMG 160 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 AMG 160 in combination with abiraterone.
Drug: AMG 160
AMG 160 will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: Abiraterone
Abiraterone will be administered orally.
Other Name: Cytochrome P450 (CYP)17 inhibitor

Experimental: AMG 160 and AMG 404: Dose Exploration
The dose-exploration part of the study will estimate the MTD/RP2D of AMG 160 in combination with AMG 404.
Drug: AMG 160
AMG 160 will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: AMG 404
AMG 404 will be administered as an intravenous (IV) infusion.
Other Name: PD-1 inhibitor

Experimental: AMG 160 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 AMG 160 in combination with AMG 404.
Drug: AMG 160
AMG 160 will be administered as an intravenous (IV) infusion.
Other Name: PSMA targeted therapy

Drug: AMG 404
AMG 404 will be administered as an intravenous (IV) infusion.
Other Name: PD-1 inhibitor

Active Comparator: AMG 404 Monotherapy
Part 3 of this study (AMG 404 monotherapy) is being conducted to evaluate the preliminary anti-tumor activity of PD-1 inhibition in the mCRPC population.
Drug: AMG 404
AMG 404 will be administered as an intravenous (IV) infusion.
Other Name: PD-1 inhibitor




Primary Outcome Measures :
  1. Number of participants who experience dose limiting toxicities (DLTs) [ Time Frame: Up to 3 years ]

    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 AMG 160. 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 AMG 160 with an evaluable DLT endpoint. 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.


  2. Number of participants who experience one or more treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  3. Number of participants who experience one or more treatment-related adverse events [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  4. Number of participants who experience a clinically significant change in vital signs [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  5. Number of participants who experience a clinically significant change in clinical laboratory tests [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study


Secondary Outcome Measures :
  1. Objective response rate per response evaluation criteria in solid tumors (RECIST) 1.1 with prostate cancer working group 3 (PCWG3) modifications [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  2. Number of participants who experience circulating tumor cell (CTC) response [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  3. Number of participants who experience prostate-specific antigen (PSA) response rate [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  4. Duration of response [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  5. Overall survival (OS) [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  6. Progression-free survival [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  7. Time to progression [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  8. Time to subsequent therapy [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  9. Maximum plasma concentration (Cmax) [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  10. Minimum plasma concentration (Cmin) [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  11. Area under the concentration-time curve (AUC) [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  12. Accumulation ratio based on area under the concentration-time curve (AUC) [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  13. Half-life (t1/2) [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  14. 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) [ Time Frame: Baseline up to 3 years ]
    Parts 1, 2 and 3 of the study

  15. 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) [ Time Frame: Baseline to 3 years ]
    Parts 1, 2 and 3 of the study

  16. Time to symptomatic skeletal events [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  17. Concentration of alkaline phosphatase [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  18. Concentration of lactate dehydrogenase (LDH) [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  19. Concentration of hemoglobin [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  20. Neutrophil-to-lymphocyte ratio [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study

  21. Concentration of N-telopeptide in the urine [ Time Frame: Up to 3 years ]
    Parts 1, 2 and 3 of the study



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

All parts

Inclusion Criteria:

  • 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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04631601


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40207
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Australia, New South Wales
St Vincents Hospital Sydney Recruiting
Darlinghurst, New South Wales, Australia, 2010
Denmark
Rigshospitalet Recruiting
Kobenhavn O, Denmark, 2100
Spain
Clinica Universidad de Navarra Recruiting
Pamplona, Navarra, Spain, 31008
Sweden
Skanes universitetssjukhus Recruiting
Lund, Sweden, 221 85
Akademiska sjukhuset Recruiting
Uppsala, Sweden, 75185
United Kingdom
Royal Marsden Hospital Recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT04631601    
Other Study ID Numbers: 20190505
2020-001305-23 ( EudraCT Number )
First Posted: November 17, 2020    Key Record Dates
Last Update Posted: July 8, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: 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.
Access Criteria: 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.
URL: http://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Amgen:
AMG 160
HALF-LIFE EXTENDED (HLE) BITE
mCRPC
Metastatic Castration-resistant Prostate Cancer
68
Gallium (68Ga)-prostate-specific membrane
antigen (PSMA)-11 positron emission
tomography(PET)/computed tomography (CT)
and
18
F-fluorodeoxyglucose (FDG) PET/CT
based response evaluation
Bispecific T cell Engager
BITE
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Androgens
Androgen Receptor Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Androgen Antagonists
Hormone Antagonists