- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01498952
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
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
6
Phase
- 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
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California
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Oxnard, California, United States, 93030
- Research Site
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Colorado
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Golden Springs, Colorado, United States, 80401
- Research Site
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Nevada
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Las Vegas, Nevada, United States, 89169
- Research Site
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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
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 |
Intervention / Treatment |
---|---|
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.
|
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
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.
|
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
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.
|
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
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.
|
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
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.
|
Sorafenib is a tyrosine kinase inhibitor, anti-angiogenic, VEGF inhibitor
|
What is the study measuring?
Primary Outcome Measures
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.
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Day 1 to Day 21 of Cycle 1
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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)
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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)
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Phase 2: Time to Progression
Time Frame: From Day 1 until documentation of progressive disease (approximately 15 months)
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Phase 2 part of the study was not launched by the sponsor due to strategic business reasons.
Therefore, this outcome was not evaluated.
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From Day 1 until documentation of progressive disease (approximately 15 months)
|
Secondary Outcome Measures
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)
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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.
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From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
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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.
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From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
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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)
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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.
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Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)
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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)
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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.
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Cycle 1 (pre-dose; and 5 minutes, 24 hours, Day 8, and Day 15 post-dose); and Cycle 2 Day 1 (pre-dose)
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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
Investigators
- 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)
January 17, 2012
Primary Completion (Actual)
April 9, 2013
Study Completion (Actual)
April 9, 2013
Study Registration Dates
First Submitted
November 29, 2011
First Submitted That Met QC Criteria
December 21, 2011
First Posted (Estimate)
December 26, 2011
Study Record Updates
Last Update Posted (Actual)
February 19, 2019
Last Update Submitted That Met QC Criteria
February 18, 2019
Last Verified
February 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Liver Neoplasms
- Carcinoma
- Carcinoma, Hepatocellular
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Sorafenib
Other Study ID 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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