Back to resultsMEDI-573 in Combination With SOC in Unresectable or Metastatic HCC. (MEDI-573-1028)
Primary Purpose
Unresectable or Metastatic Hepatocellular Carcinoma (HCC)
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MEDI-573 (1 of 3 doses)
Sorafenib
Sponsored by
About this trial
This is an interventional treatment trial for Unresectable or Metastatic Hepatocellular Carcinoma (HCC) focused on measuring HCC, liver cancer, hepatocellular carcinoma, MEDI-573, anti-IGF
Eligibility Criteria
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
Sites / Locations
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Active Comparator
Arm Label
Phase 1b Cohort A
Phase 1b Cohort B
Phase 1b Cohort C
Phase 2 Arm 1
Phase 2 Arm 2
Arm Description
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.
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.
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.
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.
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.
Outcomes
Primary Outcome Measures
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
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.
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
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).
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
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).
Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs
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).
Phase 1b: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs
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).
Phase 2: Time to Progression
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Secondary Outcome Measures
Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573
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.
Phase 2: Best Overall Tumor Response
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Phase 2: Objective Response Rate
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Phase 2: Progression-free Survival (PFS)
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Phase 2: Change in Tumor Size
Phase 2 part the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1
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.
Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1
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.
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01498952
Brief Title
MEDI-573 in Combination With SOC in Unresectable or Metastatic HCC.
Acronym
MEDI-573-1028
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
January 17, 2012 (Actual)
Primary Completion Date
April 9, 2013 (Actual)
Study Completion Date
April 9, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unresectable or Metastatic Hepatocellular Carcinoma (HCC)
Keywords
HCC, liver cancer, hepatocellular carcinoma, MEDI-573, anti-IGF
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1b Cohort A
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1b Cohort B
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 1b Cohort C
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 Arm 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase 2 Arm 2
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
MEDI-573 (1 of 3 doses)
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Intervention Description
Sorafenib is a tyrosine kinase inhibitor, anti-angiogenic, VEGF inhibitor
Primary Outcome Measure Information:
Title
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
Description
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.
Time Frame
Day 1 to Day 21 of Cycle 1
Title
Phase 1b: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (SAEs)
Description
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).
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)
Title
Phase 1b: Number of Participants With Clinical Laboratory Abnormalities Reported as TEAEs
Description
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).
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)
Title
Phase 1b: Number of Participants With Vital Signs Abnormalities Reported as TEAEs
Description
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).
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)
Title
Phase 1b: Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as TEAEs
Description
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).
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)
Title
Phase 2: Time to Progression
Description
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Time Frame
From Day 1 until documentation of progressive disease (approximately 15 months)
Secondary Outcome Measure Information:
Title
Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573
Description
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.
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)
Title
Phase 2: Best Overall Tumor Response
Description
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Title
Phase 2: Objective Response Rate
Description
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Title
Phase 2: Progression-free Survival (PFS)
Description
Phase 2 part of the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Title
Phase 2: Change in Tumor Size
Description
Phase 2 part the study was not launched by the sponsor due to strategic business reasons. Therefore, this outcome was not evaluated.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (approximately 15 months)
Title
Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1
Description
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.
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)
Title
Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1
Description
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.
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)
Title
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
Description
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.
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan Perez, MD
Organizational Affiliation
MedImmune LLC
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
Research Site
City
Golden Springs
State/Province
Colorado
ZIP/Postal Code
80401
Country
United States
Facility Name
Research Site
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
12. IPD Sharing Statement
Learn more about this trial
MEDI-573 in Combination With SOC in Unresectable or Metastatic HCC.
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