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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02991911
Recruitment Status : Completed
First Posted : December 14, 2016
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC

Tracking Information
First Submitted Date  ICMJE December 1, 2016
First Posted Date  ICMJE December 14, 2016
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE January 6, 2017
Actual Primary Completion Date September 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 21, 2018)
  • Occurrence of adverse events (AEs) [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
    Safety Endpoint
  • Occurrence of serious adverse events (SAEs) [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
    Safety Endpoint
  • Occurrence of dose-limiting toxicities (DLTs) [ Time Frame: From time of first dose through 21 days after first dose of MEDI3726 ]
    Safety Endpoint
  • Number of patients with changes in laboratory parameters from baseline [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
    Safety Endpoint
  • Number of patients with changes in vital signs from baseline [ Time Frame: From time of informed consent through 21 days after last dose of MEDI3726 ]
    Safety Endpoint
  • Number of patients with changes in electrocardiogram (ECG) results from baseline [ Time Frame: From time of informed consent through 21 days after last dose of MEDI3726 ]
    Safety Endpoint
Original Primary Outcome Measures  ICMJE
 (submitted: December 9, 2016)
  • Occurrence of adverse events (AEs) [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • Occurrence of serious adverse events (SAEs) [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • Occurrence of dose-limiting toxicities (DLTs) [ Time Frame: From time of informed consent through 21 days after first dose of MEDI3726 ]
  • Number of patients with changes in laboratory parameters from baseline [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • Number of patients with changes in vital signs from baseline [ Time Frame: From time of informed consent through 21 days after last dose of MEDI3726 ]
  • Number of patients with changes in electrocardiogram (ECG) results from baseline [ Time Frame: From time of informed consent through 21 days after last dose of MEDI3726 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2018)
  • Response Evaluation Criteria in Solid Tumors (RECIST) response [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
    Response according to RECIST version 1.1
  • PSA50 response [ Time Frame: From time of fist dose through at least 12 weeks after first dose of MEDI3726 ]
    Reduction in PSA level of 50% (PSA50) or more compared with baseline
  • Circulating Tumor Cell (CTC) response [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
    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
  • 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 ]
    Measured by occurrence of AEs, SAEs, DLTs and number of patients with changes in laboratory parameters, vital signs, and ECG results from baseline
  • MEDI3726 plasma concentrations for pharmacokinetics (PK) [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • MEDI3726 maximum observed concentration for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • MEDI3726 area under the concentration-time curve for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • MEDI3726 clearance for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • MEDI3726 terminal half-life for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • 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 ]
    To determine the immunogenicity of MEDI3726
Original Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2016)
  • Response Evaluation Criteria in Solid Tumors (RECIST) response [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
    Response according to RECIST version 1.1
  • PSA50 response [ Time Frame: From time of informed consent through at least 12 weeks after last dose of MEDI3726 ]
    Reduction in PSA level of 50% (PSA50) or more compared with baseline
  • Circulating Tumor Cell (CTC) response [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
    Conversion in the CTC count defined as a reduction from ≥ 5 cells/7.5 mL blood to < 5 cells/7.5 mL blood
  • 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 ]
    Measured by occurrence of AEs, SAEs, DLTs and number of patients with changes in laboratory parameters, vital signs, and ECG results from baseline
  • MEDI3726 plasma concentrations for pharmacokinetics (PK) [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • MEDI3726 maximum observed concentration for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • MEDI3726 area under the concentration-time curve for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • MEDI3726 clearance for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • MEDI3726 terminal half-life for PK [ Time Frame: From time of informed consent through 90 days after last dose of MEDI3726 ]
  • 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 ]
    To determine the immunogenicity of MEDI3726
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1/1b Study of MEDI3726 in Adults Subjects With Metastatic Castration Resistant Prostate Cancer
Official Title  ICMJE 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.
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Castration Resistant Prostate Cancer
Intervention  ICMJE
  • Biological: MEDI3726 Post-Chemo
    Single agent MEDI3726 after abiraterone or enzalutatmide, with a prior taxane-based chemotherapy in the mCRPC setting
  • Biological: MEDI3726 Pre-Chemo
    Single agent MEDI3726 after abiraterone or enzalutatmide, without a prior taxane-based chemotherapy in the mCRPC setting
  • Biological: MEDI3726 & Enzalutamide Combo
    MEDI3726 in combination with Enzalutatmide after prior treatment with abiraterone, with or without a prior taxane-based chemotherapy in the mCRPC setting
Study Arms  ICMJE
  • Experimental: Arm A
    MEDI3726 Post-Chemo
    Intervention: Biological: MEDI3726 Post-Chemo
  • Experimental: Arm B
    MEDI3726 Pre-Chemo
    Intervention: Biological: MEDI3726 Pre-Chemo
  • Experimental: Arm C
    MEDI3726 & Enzalutamide Combo
    Intervention: Biological: MEDI3726 & Enzalutamide Combo
Publications * Cho S, Zammarchi F, Williams DG, Havenith CEG, Monks NR, Tyrer P, D'Hooge F, Fleming R, Vashisht K, Dimasi N, Bertelli F, Corbett S, Adams L, Reinert HW, Dissanayake S, Britten CE, King W, Dacosta K, Tammali R, Schifferli K, Strout P, Korade M 3rd, Masson Hinrichs MJ, Chivers S, Corey E, Liu H, Kim S, Bander NH, Howard PW, Hartley JA, Coats S, Tice DA, Herbst R, van Berkel PH. Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer. Mol Cancer Ther. 2018 Oct;17(10):2176-2186. doi: 10.1158/1535-7163.MCT-17-0982. Epub 2018 Jul 31.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 3, 2019)
33
Original Estimated Enrollment  ICMJE
 (submitted: December 9, 2016)
224
Actual Study Completion Date  ICMJE September 30, 2019
Actual Primary Completion Date September 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02991911
Other Study ID Numbers  ICMJE D9320C00001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MedImmune LLC
Study Sponsor  ICMJE MedImmune LLC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MedImmune LLC Sponsor GmbH
PRS Account MedImmune LLC
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP