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Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Anti-tumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Metastatic Castration Resistant Prostate Cancer

NCT03724747

Description:

The study medication (BAY 2315497 Injection) is a thorium-227 labeled immuno-conjugate, specific for the prostate-specific membrane antigen (PSMA), which will be evaluated in patients with metastatic castration resistant prostate cancer. In this study, this investigational medication will be administered to patients for the first time. The primary objective of the study is to define the safety and tolerability profile and Maximal Tolerated Dose (MTD) of BAY 2315497 Injection. The secondary objectives are to determine the recommended dose for further clinical development and to investigate how the study drug is distributed and cleared from the body.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Safety, Tolerability,Pharmacokinetics, and Anti-tumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate, in Patients With Metastatic Castration Resistant Prostate Cancer
  • Official Title: A Phase 1, Open-label, First-in-human, Multi-center, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of a Thorium-227 Labeled Antibody-chelator Conjugate, BAY 2315497 Injection, in Patients With Metastatic Castration Resistant Prostate Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19445
  • SECONDARY ID: 2018-001490-25
  • NCT ID: NCT03724747

Conditions

  • Metastatic Castration Resistant Prostate Cancer (mCRPC)

Interventions

DrugSynonymsArms
BAY 2315497 InjectionDose Escalation

Purpose

The study medication (BAY 2315497 Injection) is a thorium-227 labeled immuno-conjugate, specific for the prostate-specific membrane antigen (PSMA), which will be evaluated in patients with metastatic castration resistant prostate cancer. In this study, this investigational medication will be administered to patients for the first time. The primary objective of the study is to define the safety and tolerability profile and Maximal Tolerated Dose (MTD) of BAY 2315497 Injection. The secondary objectives are to determine the recommended dose for further clinical development and to investigate how the study drug is distributed and cleared from the body.

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalThe thorium-227 dose will be escalated in a step-wise fashion to the MTD, according to a predefined dose escalation scheme. The total antibody dose of 50 mg will be evaluated first; on the basis of emerging clinical data, doses within the range of 20-100 mg may be investigated.
  • BAY 2315497 Injection
Dose expansion:Dose regimen 1ExperimentalThe thorium-227 and total antibody doses, as well as the treatment regimen, will be selected for expansion on the basis of the safety, PK and overall benefit risk profile of BAY 2315497 Injection, observed in the course of the dose escalation.
  • BAY 2315497 Injection
Dose expansion:Dose regimen 2ExperimentalThe thorium-227 and total antibody doses, as well as the treatment regimen, will be selected for expansion on the basis of the safety, PK and overall benefit risk profile of BAY 2315497 Injection, observed in the course of the dose escalation.
  • BAY 2315497 Injection

Eligibility Criteria

        Inclusion Criteria

          -  Ability to understand and sign an approved informed consent form.

          -  Male adult patients (≥ 18 years of age).

          -  ECOG PS of 0 or 1.

          -  Life expectancy ≥ 6 months.

          -  Histological, pathological and/or cytological confirmation of adenocarcinoma of the
             prostate without small cell or neuroendocrine features.

          -  Previous treatment with at least one novel androgen axis drug (NAAD) (e.g.
             enzalutamide and/or abiraterone).

          -  Patients must have prior orchiectomy and/or ongoing androgen deprivation therapy and a
             castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L).

          -  Previous treatment with at least 1, but no more than 2 previous - taxane regimens. A
             taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a patient
             has received only 1 taxane regimen, he is eligible, if refuses to receive a second
             taxane regimen, or is considered unsuitable to receive a second taxane regimen (e.g.
             intolerance).

          -  Documented progression of mCRPC, as defined according to the Prostate Cancer Working
             Group 3 (PCWG3) guidelines.

          -  Adequate bone marrow, liver, and renal function, as assessed by the following
             laboratory requirements, to be conducted within 14 days before start of study drug
             administration:

               -  Hemoglobin > 9.0 g/dL

               -  Absolute neutrophil count (ANC) > 1500/mm3

               -  White blood cell (WBC) count > 3000/mL

               -  Platelet count > 100,000 /mm*3

               -  Total bilirubin < 1,5 x upper limit of normal (ULN) (except if confirmed history
                  of Gilbert's disease)

               -  ALT and AST ≤ 2.5 x ULN

               -  Serum creatinine ≤ 1.5 X ULN and glomerular filtration rate (GFR ≥ 45 mL/min/1.73
                  m2, according to the MDRD (Modified Diet in Renal Disease) abbreviated formula.

          -  Patients with partners of childbearing potential must be willing to use highly
             effective methods of birth control for the time period between the first
             administration of BAY 2315497 Injection to at least 6 months after the last
             administration of the study drug.

        Exclusion Criteria

          -  Diffuse bone or bone-marrow involvement (i.e. "superscan").

          -  Spinal cord compression or known brain metastases.

          -  Known incompatibility to CT/MRI, bone scan or uncontrolled pain, which results in
             patient's lack of compliance with the CT/MRI and bone scan required for PCWG3 tumor
             assessment.

          -  Clinically significant heart disease, as evidenced by myocardial infarction, arterial
             thrombotic events in the past 6 months, severe or unstable angina, or uncontrolled
             cardiovascular history.

          -  Patients known to be affected by genetic defects linked to radiation Hypersensitivity.

          -  Known history of myelodysplastic syndrome (MDS) / leukemia or with features suggestive
             of MDS/AML at any time point.

          -  Concurrent or active cancer within the last 2 years with a distinct primary site or
             histology from the cancer being evaluated in this study, with the exception of cancer
             types with less than 30% likelihood of recurrence.

          -  Known allergies, hypersensitivity, or intolerance to the study drug including
             excipients, or to contrast agents used in the diagnostic or exploratory imaging
             procedures required per protocol.

          -  Any infection of National Cancer Institute Common Terminology Criteria for Adverse
             Events (NCI-CTCAE) Version 5.0 Grade ≥ 2.

          -  Known human immunodeficiency virus (HIV) infection.

          -  Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV)
             infection requiring treatment.

          -  Serious, non-healing wound, ulcer, or bone fracture.

          -  Any systemic anti-neoplastic therapy (e.g. chemotherapy, immunotherapy or biological
             therapy [including monoclonal antibodies], PARP inhibitors) within at least 30 days
             prior to day of randomization (except for Luteinizing Hormone-releasing Hormone [LHRH]
             or Gonadotropin-releasing Hormone [GnRH]).

          -  Previous high-dose chemotherapy, needing hemopoietic stem cell rescue, is prohibited.

          -  Prior major surgery (excluding prostatic biopsies) must be at least 12 weeks prior to
             study entry.

          -  Previous treatment with therapeutic PSMA-targeted agents.

          -  Previous treatment with radium-223 dichloride or other radiopharmaceuticals, including
             but not limited to strontium-89 or samarium-153.

          -  Prior definitive radiotherapy completed less than 6 weeks before start of the study
             drug administration.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) of BAY 2315497 injection
Time Frame:Cycle 1 (42 days)
Safety Issue:
Description:The maximum dose at which the incidence of DLTs occurring during Cycle 1 is below 30%.

Secondary Outcome Measures

Measure:Recommended dose for further clinical development of BAY 2315497 injection
Time Frame:Up to 6 cycles (each cycle is 42 days, a maximum of 3 additional treatment cycles may be administered in case a favorable benefit risk profile is documented)
Safety Issue:
Description:The dose / regimen recommended for further clinical development will be defined after evaluation of the safety, PK and overall clinical data, collected in cycle 1 and subsequent cycles, in the dose escalation and dose expansion parts of the study.
Measure:Maximum observed concentration (Cmax) of thorium
Time Frame:Cycle 1 (From day 1 to 43)
Safety Issue:
Description:
Measure:Area under the curve from time of dosing to 42 days after dosing [AUC(0-42)] days of thorium
Time Frame:Cycle 1 (From day 1 to 43)
Safety Issue:
Description:
Measure:Cmax of radium
Time Frame:Cycle 1 (From day 1 to 43)
Safety Issue:
Description:
Measure:AUC(0-42) days of radium
Time Frame:Cycle 1 (From day 1 to 43)
Safety Issue:
Description:
Measure:Cmax of total antibody
Time Frame:Cycle 1 (From day 1 to 43)
Safety Issue:
Description:
Measure:AUC(0-42) days of total antibody
Time Frame:Cycle 1 (From day 1 to 43)
Safety Issue:
Description:

Details

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

Trial Keywords

  • Metastatic castration resistant prostate cancer, thorium-227, targeted alpha therapy,PSMA

Last Updated

November 7, 2019