Clinical Trials /

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

NCT04631601

Description:

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

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 20190505
  • SECONDARY ID: 2020-001305-23
  • NCT ID: NCT04631601

Conditions

  • Metastatic Castration-resistant Prostate Cancer

Interventions

DrugSynonymsArms
AMG 160PSMA targeted therapyAMG 160 and AMG 404: Dose Expansion
EnzalutamideAndrogen receptor inhibitorAMG 160 and Enzalutamide: Dose Expansion
AbirateroneCytochrome P450 (CYP)17 inhibitorAMG 160 and Abiraterone: Dose Expansion
AMG 404PD-1 inhibitorAMG 160 and AMG 404: Dose Expansion

Purpose

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

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).
    

Trial Arms

NameTypeDescriptionInterventions
AMG 160 and Enzalutamide: Dose ExplorationExperimentalThe dose-exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of AMG 160 in combination with enzalutamide.
  • AMG 160
  • Enzalutamide
AMG 160 and Enzalutamide: Dose ExpansionExperimentalFollowing 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.
  • AMG 160
  • Enzalutamide
AMG 160 and Abiraterone: Dose ExplorationExperimentalThe dose exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of AMG 160 in combination with abiraterone.
  • AMG 160
  • Abiraterone
AMG 160 and Abiraterone: Dose ExpansionExperimentalFollowing 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.
  • AMG 160
  • Abiraterone
AMG 160 and AMG 404: Dose ExplorationExperimentalThe dose-exploration part of the study will estimate the MTD/RP2D of AMG 160 in combination with AMG 404.
  • AMG 160
  • AMG 404
AMG 160 and AMG 404: Dose ExpansionExperimentalFollowing 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.
  • AMG 160
  • AMG 404
AMG 404 MonotherapyActive ComparatorPart 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.
  • AMG 404

Eligibility 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
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants who experience dose limiting toxicities (DLTs)
Time Frame:Up to 3 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Number of participants who experience circulating tumor cell (CTC) response
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Number of participants who experience prostate-specific antigen (PSA) response rate
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Duration of response
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Overall survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Progression-free survival
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Time to progression
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Time to subsequent therapy
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Maximum plasma concentration (Cmax)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Minimum plasma concentration (Cmin)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Area under the concentration-time curve (AUC)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Accumulation ratio based on area under the concentration-time curve (AUC)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Half-life (t1/2)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure: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
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure: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
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Time to symptomatic skeletal events
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Concentration of alkaline phosphatase
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Concentration of lactate dehydrogenase (LDH)
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Concentration of hemoglobin
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Neutrophil-to-lymphocyte ratio
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study
Measure:Concentration of N-telopeptide in the urine
Time Frame:Up to 3 years
Safety Issue:
Description:Parts 1, 2 and 3 of the study

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

  • 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

Last Updated

March 29, 2021