MEDI-573 in Combination With SOC in Unresectable or Metastatic HCC. (MEDI-573-1028)

February 18, 2019 updated by: MedImmune LLC

A Phase 1b/2, Open-label, Randomized Study of MEDI-573 in Combination With Sorafenib Verses Sorafenib Alone in Adult Subjects With Unresectable or Metastatic Hepatocellular Carcinoma

A Phase 1b/2, open-label, randomized study to evaluate MEDI-573 in combination with standard of care in adult subjects with unresectable or metastatic hepatocellular carcinoma (HCC).

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.
6

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

  • United States
    • California
      • Oxnard, California, United States, 93030
        • Research Site
    • Colorado
      • Golden Springs, Colorado, United States, 80401
        • Research Site
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • 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

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥ 18 years or minimum age of consent per local regulations at the time of screening
  • Unresectable or metastatic hepatocellular carcinoma
  • ECOG Performance Status ≤ 2
  • Life expectancy of ≥ 3 months;

Exclusion Criteria:

  • Child-Pugh Score for Cirrhosis Mortality > 7 points
  • Prior or current system anti-cancer therapy for HCC, including cytotoxic, biologic, targeted or experimental therapy
  • Prior local treatment for HCC less than 4 weeks prior to initiating study treatment
  • Active second malignancy
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks prior to initiating study treatment
  • Thrombotic or embolic events within 6 months prior to initiating study treatment
  • Ongoing pancreatitis
  • Uncontrolled or refractory ascites
  • Evidence of ongoing spinal cord compression, known carcinomatous meningitis, or known leptomeningeal carcinomatosis
  • Hepatic encephalopathy > Grade 1
  • Active brain metastases with exceptions
  • Poorly controlled diabetes mellitus
  • Active coronary artery disease
  • Uncontrolled hypertension

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: Randomized
  • Interventional Model: Parallel 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: Phase 1b Cohort A
Participants will receive MEDI-573 10 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
Drug: MEDI-573 (1 of 3 doses)
MEDI-573, a human immunoglobulin G2 lambda (IgG2λ) monoclonal antibody (MAb), is a dual-targeting human antibody that neutralizes insulin-like growth factor (IGF)-I and IGF-II ligands
Drug: Sorafenib
Sorafenib is a tyrosine kinase inhibitor, anti-angiogenic, VEGF inhibitor
Experimental: Phase 1b Cohort B
Participants will receive MEDI-573 45 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
Drug: MEDI-573 (1 of 3 doses)
MEDI-573, a human immunoglobulin G2 lambda (IgG2λ) monoclonal antibody (MAb), is a dual-targeting human antibody that neutralizes insulin-like growth factor (IGF)-I and IGF-II ligands
Drug: Sorafenib
Sorafenib is a tyrosine kinase inhibitor, anti-angiogenic, VEGF inhibitor
Experimental: Phase 1b Cohort C
Participants will receive MEDI-573 30 mg/kg intravenous infusion on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
Drug: MEDI-573 (1 of 3 doses)
MEDI-573, a human immunoglobulin G2 lambda (IgG2λ) monoclonal antibody (MAb), is a dual-targeting human antibody that neutralizes insulin-like growth factor (IGF)-I and IGF-II ligands
Drug: Sorafenib
Sorafenib is a tyrosine kinase inhibitor, anti-angiogenic, VEGF inhibitor
Experimental: Phase 2 Arm 1
Participants will receive recommended dose of MEDI-573 from Phase 1b IV on Day 1 of each 21-day cycle and sorafenib 400 mg orally twice daily as background therapy until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
Drug: MEDI-573 (1 of 3 doses)
MEDI-573, a human immunoglobulin G2 lambda (IgG2λ) monoclonal antibody (MAb), is a dual-targeting human antibody that neutralizes insulin-like growth factor (IGF)-I and IGF-II ligands
Drug: Sorafenib
Sorafenib is a tyrosine kinase inhibitor, anti-angiogenic, VEGF inhibitor
Active Comparator: Phase 2 Arm 2
Participants will receive sorafenib 400 mg orally twice daily until unacceptable toxicity, documentation of disease progression, initiation of alternative anticancer treatment, or withdrawal for other reasons.
Drug: Sorafenib
Sorafenib is a tyrosine kinase inhibitor, anti-angiogenic, VEGF inhibitor

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
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
Time Frame: Day 1 to Day 21 of Cycle 1
The DLT was defined as any Grade 3 or higher hematologic or non-hematologic toxicity considered to be related to MEDI-573 that occurred during the DLT evaluation period (Days 1 to 21 of Cycle 1), with the exceptions of Grade 3 fever (occurred in the absence of neutropenia and resolved to normal or baseline within 24 hours of treatment and was not considered as SAE), Grade 3 rigors/chills that responded to optimal therapy, and Grade < 4 hyperglycemia that resolved in < 24 hours.
Day 1 to Day 21 of Cycle 1
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
Time Frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
An Adverse Event (AE) is any unfavourable and unintended sign, symptoms, or diseases temporally associated with use of study drug, whether or not considered related to study drug. A serious adverse event (SAE) is an AE that results in death, initial or prolonged inpatient hospitalization, life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or an important medical event. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Time Frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs
Time Frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
An abnormal vital signs that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
Phase 1b: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs
Time Frame: From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
An abnormal ECG findings that were judged by the investigator to be medically significant were reported as AEs. The TEAEs are defined as AEs present at baseline that worsened in intensity after administration of study drug, or events absent at baseline that emerged after administration of study drug, up to 60 days after the last study drug or until the participants started another anticancer therapy, whichever occurred first (approximately 15 months).
From the start of study treatment (Day 1) through 60 days after the last dose of MEDI-573 or initiation of another anticancer therapy, whichever occurred first (approximately 15 months)
Phase 2: Time to Progression
Time Frame: From Day 1 until documentation of progressive disease (approximately 15 months)
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
From Day 1 until documentation of progressive disease (approximately 15 months)

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
Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573
Time Frame: Predose on Day 1 of every treatment cycle; end of treatment; Days 30, 60 and 90 post treatment; every 3 months post treatrment till end of study (approximately 15 months)
Participants with positive ADA to MEDI-573 are reported in the below table. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.
Predose on Day 1 of every treatment cycle; end of treatment; Days 30, 60 and 90 post treatment; every 3 months post treatrment till end of study (approximately 15 months)
Phase 2: Best Overall Tumor Response
Time Frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Phase 2: Objective Response Rate
Time Frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Phase 2: Progression-free Survival (PFS)
Time Frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Phase 2: Change in Tumor Size
Time Frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Phase 2 part the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1
Time Frame: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)
The tmax is defined as actual sampling time to reach maximum observed serum concentration of the study drug. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.
Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)
Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1
Time Frame: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)
The Cmax is the maximum observed serum concentration of study drug. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.
Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)
Phase 1b and Phase 2: Area Under Serum Concentration-time Curve From Time Zero to Day 22 (AUC0-Day22) of MEDI-573 for Cycle 1
Time Frame: Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)
Area under the concentration-time curve from time zero to Day 22 is reported. This outcome was not evaluated for Phase 2 as it was not launched by the sponsor due to strategic business reasons.
Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)

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

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Susan Perez, MD, MedImmune LLC

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 17, 2012

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.
April 9, 2013

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.
April 9, 2013

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).
November 29, 2011

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 21, 2011

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 26, 2011

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.
February 19, 2019

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.
February 18, 2019

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.
February 1, 2019

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.
  • CD-ON-MEDI-573-1028

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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