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

January 14, 2020 updated by: MedImmune LLC

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.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
33

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Chur, Switzerland, 7000
        • Research Site
  • United Kingdom
      • London, United Kingdom, SM2 5PT
        • Research Site
  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Research Site
    • Florida
      • Sarasota, Florida, United States, 34232
        • Research Site
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 96 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm A
MEDI3726 Post-Chemo
Biological: MEDI3726 Post-Chemo
Single agent MEDI3726 after abiraterone or enzalutatmide, with a prior taxane-based chemotherapy in the mCRPC setting
Experimental: Arm B
MEDI3726 Pre-Chemo
Biological: MEDI3726 Pre-Chemo
Single agent MEDI3726 after abiraterone or enzalutatmide, without a prior taxane-based chemotherapy in the mCRPC setting
Experimental: Arm C
MEDI3726 & Enzalutamide Combo
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Occurrence of adverse events (AEs)
Time Frame: From time of informed consent through 90 days after last dose of MEDI3726
Safety Endpoint
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
Safety Endpoint
From time of informed consent through 90 days after last dose of MEDI3726
Occurrence of dose-limiting toxicities (DLTs)
Time Frame: From time of first dose through 21 days after first dose of MEDI3726
Safety Endpoint
From time of first dose 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
Safety Endpoint
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
Safety Endpoint
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
Safety Endpoint
From time of informed consent through 21 days after last dose of MEDI3726

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
From time of informed consent through 90 days after last dose of MEDI3726
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
From time of fist dose through at least 12 weeks after first dose of MEDI3726
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
From time of informed consent through 90 days after last dose of MEDI3726
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
From time of informed consent through 90 days after last dose of MEDI3726 with enzalutamide
MEDI3726 plasma concentrations for pharmacokinetics (PK)
Time Frame: From time of informed consent through 90 days after last dose of MEDI3726
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
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
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
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
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
From time of informed consent through 90 days after last dose of MEDI3726

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
MedImmune LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 6, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 1, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 14, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 18, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 14, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D9320C00001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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