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A Phase 1/1b Study of MEDI3726 in Adults Subjects With Metastatic Castration Resistant Prostate Cancer

NCT02991911

Description:

The purpose of this study is to assess the safety and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI3726 in subjects with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1/1b Study of MEDI3726 in Adults Subjects With Metastatic Castration Resistant Prostate Cancer
  • Official Title: A Phase 1/1b Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI3726 in Subjects With Metastatic Castration Resistant Prostate Cancer Who Have Received Prior Treatment With Abiraterone or Enzalutamide.

Clinical Trial IDs

  • ORG STUDY ID: D9320C00001
  • NCT ID: NCT02991911

Conditions

  • Metastatic Castration Resistant Prostate Cancer

Interventions

DrugSynonymsArms
MEDI3726 Post-ChemoArm A
MEDI3726 Pre-ChemoArm B
MEDI3726 & Enzalutamide ComboArm C

Purpose

The purpose of this study is to assess the safety and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI3726 in subjects with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting.

Trial Arms

NameTypeDescriptionInterventions
Arm AExperimentalMEDI3726 Post-Chemo
  • MEDI3726 Post-Chemo
Arm BExperimentalMEDI3726 Pre-Chemo
  • MEDI3726 Pre-Chemo
Arm CExperimentalMEDI3726 & Enzalutamide Combo
  • MEDI3726 & Enzalutamide Combo

Eligibility Criteria

        Inclusion Criteria:

          -  Age ≥ 18 years at the time of screening.

          -  Histologically confirmed diagnosis of metastatic castration-resistant prostate
             adenocarcinoma (mCRPC).

          -  Documented PD in subjects with mCRPC as assessed by the Investigator and defined by at
             least one of the following according to the PCWG3 criteria:

               1. Radiographic progression.

               2. PSA progression.

          -  Prior exposure to abiraterone or enzalutamide of at least 12 weeks in the mCRPC
             setting.

        NOTE: Subjects who have received both abiraterone and enzalutamide in the mCRPC setting are
        eligible.

          -  In dose escalation: Prior taxane-based chemotherapy in the mCRPC setting is:

               1. Required for Arm A.

               2. Excluded for Arm B.

               3. Optional for Arm C.

                  Exclusion Criteria:

          -  Subjects with neuroendocrine, neuroendocrine differentiation and/or small cell
             prostate cancer.

          -  The subject has received any conventional or investigational anti-cancer treatment
             within 21 days before the first dose of investigational product, with the following
             modifications:

               1. At least 14 days before the first dose of investigational product since
                  completion of treatment with abiraterone or enzalutamide

               2. At least 14 days before the first dose of investigational product since
                  completion of prior taxane-based chemotherapy

               3. At least 28 days before the first dose of investigational product since
                  completion of treatment with Radium-223.

               4. At least 42 days before the first dose of investigational product since
                  completion of prior bicalutamide and nilutamide treatment.

        NOTE: An LHRH agonist or antagonist required for ongoing testosterone suppression will be
        permitted if Inclusion Criterion is satisfied.

          -  Prior exposure to PSMA-directed therapies.

          -  Subjects with previous radiotherapy for the treatment of unresectable, locally
             advanced or metastatic prostate cancer are excluded if:

               1. More than 25% of marrow-bearing bone has been irradiated.

               2. The last fraction of radiotherapy has been administered within approximately 2
                  weeks prior to the first dose of investigational product.

          -  Brain metastases that are untreated, symptomatic, or require therapy to control
             symptoms; or any radiation, surgery, or other therapy to control symptoms from brain
             metastases within 2 months prior to the first dose of investigational product.

          -  Subjects with known history of peripheral vasculopathies including, but not limited
             to, macro and microangiopathies secondary to diabetes, peripheral arteriopathy of any
             cause, intermittent claudication, repeated and/or non-healing ulcers of any cause.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

Measure:Occurrence of adverse events (AEs)
Time Frame:From time of informed consent through 90 days after last dose of MEDI3726
Safety Issue:
Description:Safety Endpoint

Secondary Outcome Measures

Measure:Response Evaluation Criteria in Solid Tumors (RECIST) response
Time Frame:From time of informed consent through 90 days after last dose of MEDI3726
Safety Issue:
Description:Response according to RECIST version 1.1
Measure:PSA50 response
Time Frame:From time of fist dose through at least 12 weeks after first dose of MEDI3726
Safety Issue:
Description:Reduction in PSA level of 50% (PSA50) or more compared with baseline
Measure:Circulating Tumor Cell (CTC) response
Time Frame:From time of informed consent through 90 days after last dose of MEDI3726
Safety Issue:
Description:Conversion in the CTC count defined as a reduction from ≥ 5 cells/7.5 mL blood to < 5 cells/7.5 mL blood with a confirmatory assessment at least 4 weeks later
Measure:Safety and tolerability of MEDI3726 in combination with Enzalutamide
Time Frame:From time of informed consent through 90 days after last dose of MEDI3726 with enzalutamide
Safety Issue:
Description:Measured by occurrence of AEs, SAEs, DLTs and number of patients with changes in laboratory parameters, vital signs, and ECG results from baseline
Measure:MEDI3726 plasma concentrations for pharmacokinetics (PK)
Time Frame:From time of informed consent through 90 days after last dose of MEDI3726
Safety Issue:
Description:
Measure:MEDI3726 maximum observed concentration for PK
Time Frame:From time of informed consent through 90 days after last dose of MEDI3726
Safety Issue:
Description:
Measure:MEDI3726 area under the concentration-time curve for PK
Time Frame:From time of informed consent through 90 days after last dose of MEDI3726
Safety Issue:
Description:
Measure:MEDI3726 clearance for PK
Time Frame:From time of informed consent through 90 days after last dose of MEDI3726
Safety Issue:
Description:
Measure:MEDI3726 terminal half-life for PK
Time Frame:From time of informed consent through 90 days after last dose of MEDI3726
Safety Issue:
Description:
Measure:Number and percentage of subjects who develop anti-drug antibodies (ADAs)
Time Frame:From time of informed consent through 90 days after last dose of MEDI3726
Safety Issue:
Description:To determine the immunogenicity of MEDI3726

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:MedImmune LLC

Trial Keywords

  • metastatic, prostate cancer

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