Back to resultsStudy of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer
Primary Purpose
Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
MEDI-573
Aromatase Inhibitor
Sponsored by
About this trial
This is an interventional treatment trial for Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer focused on measuring MEDI-573, breast cancer, metastatic, aromatase inhibitor, anti-IGF
Eligibility Criteria
Inclusion Criteria:
- Histologically-confirmed MBC not deemed amenable to curative surgery or curative radiation therapy
- Tumors are positive for ER, PgR, or both
- Tumors must be negative for HER2 (by FISH, CISH or IHC)
- Female gender and age ≥ 18 years at time of study entry
- Postmenopausal
- Karnofsky Performance Status ≥ 70
- Life expectancy of ≥ 6 months
Exclusion Criteria:
Subjects who received prior chemotherapy, hormonal therapy, immunotherapy or biologic therapy for advanced or metastatic disease with the following exceptions:
- Prior adjuvant therapy with an AI and/or tamoxifen is allowed, provided treatment ended at least 2 weeks prior to the first dose of MEDI-573
- Prior neoadjuvant and/or adjuvant chemotherapy for breast cancer is allowed
- Extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor, or disease that is considered by the investigator to be rapidly progressing or life threatening (eg, subjects who are intended for chemotherapy)
- Active brain metastases with the exception of subject has been treated and are asymptomatic and there has been no evidence of CNS progression for at least 4 weeks of first dose of MEDI-573
- Evidence of ongoing spinal cord compression or leptomeningeal carcinomatosis
- Unresolved toxicities from prior therapy with the exception of alopecia that have not resolved to ≤ Grade 1 at the time of starting study treatment
- Previous treatment with agents that target the IGF receptor
- History of allergy or reaction attributed to compounds of chemical or biologic composition similar to those of MEDI-573 or AI
- History of another invasive malignancy within 5 years except for curatively resected nonmelanoma skin cancer or carcinoma in situ of the cervix
- Poorly controlled diabetes mellitus
Sites / Locations
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Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
MEDI-573 10 mg/kg + AI
MEDI-573 30 mg/kg + AI
MEDI-573 45 mg/kg + AI
Aromatase Inhibitor
Arm Description
Participants who will be enrolled in Phase 1b Cohort A of the study will receive intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Participants who will be enrolled in Phase 1b Cohort B of the study will receive intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Participants who will be enrolled in Phase 1b Cohort C and Phase 2 Arm 1 of the study will receive intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Participants who will be enrolled in Phase 2 Arm 2 of the study will receive oral AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Outcomes
Primary Outcome Measures
Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
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. TEAEs and TESAEs are defined as AEs and SAEs 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 occurs first (approximately 8 years).
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
The AEs that occurred during Cycle 1 (Days 1 to 21) and were suspected of having a causal relationship to MEDI-573 and were >= Grade 3 in severity were considered as DLTs.
Phase 1b: Number of DLTs
The AEs that occurred during Cycle 1 (Days 1 to 21) and were suspected of having a causal relationship to MEDI-573 and were >= Grade 3 in severity were considered as DLTs.
Phase 2: Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the time from the randomization until the first documentation of disease progression or death due to any cause, whichever occurred first.
The PFS was censored on the date of the last tumor assessment documenting absence of tumor progression for participants who had no documented progression and were still alive prior to data cut-off, dropout, or the initiation of alternate anticancer treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as >= 20% increase in the sum of diameters of target lesions and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of non-target lesions or a new lesion.
Secondary Outcome Measures
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results 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 occurs first (approximately 8 years).
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs 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 occurs first (approximately 8 years).
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) 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 occurs first (approximately 8 years).
Phase 2: Number of Participants With Best Overall Tumor Response
Tumor evaluation was based on RECIST v1.1 by CT or MRI scan as: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of target lesions and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of non-target lesions or a new lesion; not evaluable (NE): either no or only a subset of lesion measurements are made at an assessment.
Phase 2: Objective Response Rate (ORR)
The ORR was defined as percentage of participants with confirmed complete response or confirmed partial response, where CR was defined as disappearance of all target and non-target lesions and no new lesions and PR was definded as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.
Phase 2: Time to Response
Time to response was measured from treatment start to the first documentation of disease response and was evaluated only in participants who achieved objective response (confirmed CR or confirmed PR. The CR was defined as disappearance of all target and non-target lesions and no new lesions and PR was defined as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.
Phase 2: Duration of Response (DR)
Duration of response (DR) is measured from the first documentation of disease response to the first documented progressive disease and was evaluated only in participants who achieved objective response (confirmed CR or confirmed PR). The CR was defined as disappearance of all target and non-target lesions and no new lesions and PR was defined as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.
Phase 2: Time to Progression (TTP)
Time to progression was measured from treatment start until the first documentation of disease progression. The PD was defined as >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of non-target lesions or a new lesion.
Phase 2: Overall Survival (OS)
Overall survival (OS) was measured from treatment start until death.
Phase 2: Change in Tumor Size
Mean change in tumor size is reported.
Phase 1b and Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to Day 21 (AUC0-day21) of MEDI-573 for Cycle 1
AUC0-day21 of MEDI-573 for Cycle 1 is reported.
Phase 1b and Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI-573 for Cycle 1
AUC0-info of MEDI-573 for Cycle 1 is reported.
Phase 1b and Phase 2: Dose-Normalised Area Under the Serum Concentration-time Curve From Time Zero to Infinity (DN AUC0-inf) of MEDI-573 for Cycle 1
DN AUC0-inf of MEDI-573 for Cycle 1 is reported.
Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1
Cmax of MEDI-573 for Cycle 1 is reported.
Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1
Tmax of MEDI-573 for Cycle 1 is reported.
Phase 1b and Phase 2: Systemic Clearance (CL) of MEDI-573 for Cycle 1
The CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by AUC(0-infinity).
Phase 1b and Phase 2: Terminal Half Life (t1/2) of MEDI-573 for Cycle 1
The elimination half-life (t1/2) is the time measured for the serum concentration of MEDI-573 to decrease by 1 half to its original concentration.
Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II
The mean concentration profiles of both IGF-I and IGF-II post administration of MEDI-573 in plasma were evaluated during treatment.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01446159
Brief Title
Study of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer
Official Title
A Phase 1b/2 Randomized Study of MEDI-573 in Combination With an Aromatase Inhibitor (AI) Versus AI Alone in Women With Metastatic Breast Cancer (MBC)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2020
Overall Recruitment Status
Completed
Study Start Date
June 13, 2011 (Actual)
Primary Completion Date
June 28, 2019 (Actual)
Study Completion Date
June 28, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MedImmune LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Study to evaluate the safety, tolerability, antitumor activity, and pharmacology of MEDI-573 in combination with an aromatase inhibitor (AI) in adult subjects with HR+, HER2-negative MBC.
Detailed Description
This is a Phase 1b/2, multicenter, open-label study to evaluate the safety, tolerability, antitumor activity, and pharmacology of MEDI-573 in combination with an AI in adult subjects with HR+, HER2-negative MBC. This study has 2 phases: a dose-evaluation phase (Phase 1b) and a randomization phase (Phase 2).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer
Keywords
MEDI-573, breast cancer, metastatic, aromatase inhibitor, anti-IGF
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
188 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MEDI-573 10 mg/kg + AI
Arm Type
Experimental
Arm Description
Participants who will be enrolled in Phase 1b Cohort A of the study will receive intravenous infusion of MEDI-573 10 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Arm Title
MEDI-573 30 mg/kg + AI
Arm Type
Experimental
Arm Description
Participants who will be enrolled in Phase 1b Cohort B of the study will receive intravenous infusion of MEDI-573 30 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Arm Title
MEDI-573 45 mg/kg + AI
Arm Type
Experimental
Arm Description
Participants who will be enrolled in Phase 1b Cohort C and Phase 2 Arm 1 of the study will receive intravenous infusion of MEDI-573 45 mg/kg on Day 1 of each 21-day cycle and AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Arm Title
Aromatase Inhibitor
Arm Type
Experimental
Arm Description
Participants who will be enrolled in Phase 2 Arm 2 of the study will receive oral AI of the investigator's choice (letrozole, anastrozole, or exemestane) orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Intervention Type
Drug
Intervention Name(s)
MEDI-573
Intervention Description
Intravenous infusion of MEDI-573 (10 or 30 or 45 mg/kg) will be administered on Day 1 of each 21-day cycle until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Intervention Type
Drug
Intervention Name(s)
Aromatase Inhibitor
Intervention Description
Aromatase inhibitor of the investigator's choice (letrozole, anastrozole, or exemestane) will be provided orally once daily until unacceptable toxicity, documentation of disease progression, or withdrawal for other reasons.
Primary Outcome Measure Information:
Title
Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
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. TEAEs and TESAEs are defined as AEs and SAEs 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 occurs first (approximately 8 years).
Time Frame
From the start of study treatment (Day 1) through 60 days after the last dose of treatment or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years)
Title
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
Description
The AEs that occurred during Cycle 1 (Days 1 to 21) and were suspected of having a causal relationship to MEDI-573 and were >= Grade 3 in severity were considered as DLTs.
Time Frame
Up to Day 21 of Cycle 1
Title
Phase 1b: Number of DLTs
Description
The AEs that occurred during Cycle 1 (Days 1 to 21) and were suspected of having a causal relationship to MEDI-573 and were >= Grade 3 in severity were considered as DLTs.
Time Frame
Up to Day 21 of Cycle 1
Title
Phase 2: Progression-free Survival (PFS)
Description
Progression-free survival (PFS) was defined as the time from the randomization until the first documentation of disease progression or death due to any cause, whichever occurred first.
The PFS was censored on the date of the last tumor assessment documenting absence of tumor progression for participants who had no documented progression and were still alive prior to data cut-off, dropout, or the initiation of alternate anticancer treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as >= 20% increase in the sum of diameters of target lesions and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of non-target lesions or a new lesion.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Secondary Outcome Measure Information:
Title
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results 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 occurs first (approximately 8 years).
Time Frame
From the start of study treatment (Day 1) through 60 days after the last dose of treatment or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years)
Title
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs 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 occurs first (approximately 8 years).
Time Frame
From the start of study treatment (Day 1) through 60 days after the last dose of treatment or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years)
Title
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) 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 occurs first (approximately 8 years).
Time Frame
From the start of study treatment (Day 1) through 60 days after the last dose of treatment or until the participants started another anticancer therapy, whichever occurs first (approximately 8 years)
Title
Phase 2: Number of Participants With Best Overall Tumor Response
Description
Tumor evaluation was based on RECIST v1.1 by CT or MRI scan as: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new lesions; Stable disease (SD): Neither sufficient shrinkage to qualify as a response nor sufficient growth to qualify as progression; Progressive Disease (PD): >= 20% increase in the sum of diameters of target lesions and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of non-target lesions or a new lesion; not evaluable (NE): either no or only a subset of lesion measurements are made at an assessment.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Title
Phase 2: Objective Response Rate (ORR)
Description
The ORR was defined as percentage of participants with confirmed complete response or confirmed partial response, where CR was defined as disappearance of all target and non-target lesions and no new lesions and PR was definded as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Title
Phase 2: Time to Response
Description
Time to response was measured from treatment start to the first documentation of disease response and was evaluated only in participants who achieved objective response (confirmed CR or confirmed PR. The CR was defined as disappearance of all target and non-target lesions and no new lesions and PR was defined as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Title
Phase 2: Duration of Response (DR)
Description
Duration of response (DR) is measured from the first documentation of disease response to the first documented progressive disease and was evaluated only in participants who achieved objective response (confirmed CR or confirmed PR). The CR was defined as disappearance of all target and non-target lesions and no new lesions and PR was defined as >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Title
Phase 2: Time to Progression (TTP)
Description
Time to progression was measured from treatment start until the first documentation of disease progression. The PD was defined as >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of non-target lesions or a new lesion.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Title
Phase 2: Overall Survival (OS)
Description
Overall survival (OS) was measured from treatment start until death.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Title
Phase 2: Change in Tumor Size
Description
Mean change in tumor size is reported.
Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Title
Phase 1b and Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to Day 21 (AUC0-day21) of MEDI-573 for Cycle 1
Description
AUC0-day21 of MEDI-573 for Cycle 1 is reported.
Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Title
Phase 1b and Phase 2: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI-573 for Cycle 1
Description
AUC0-info of MEDI-573 for Cycle 1 is reported.
Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Title
Phase 1b and Phase 2: Dose-Normalised Area Under the Serum Concentration-time Curve From Time Zero to Infinity (DN AUC0-inf) of MEDI-573 for Cycle 1
Description
DN AUC0-inf of MEDI-573 for Cycle 1 is reported.
Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Title
Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1
Description
Cmax of MEDI-573 for Cycle 1 is reported.
Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Title
Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1
Description
Tmax of MEDI-573 for Cycle 1 is reported.
Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Title
Phase 1b and Phase 2: Systemic Clearance (CL) of MEDI-573 for Cycle 1
Description
The CL is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by AUC(0-infinity).
Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Title
Phase 1b and Phase 2: Terminal Half Life (t1/2) of MEDI-573 for Cycle 1
Description
The elimination half-life (t1/2) is the time measured for the serum concentration of MEDI-573 to decrease by 1 half to its original concentration.
Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Title
Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II
Description
The mean concentration profiles of both IGF-I and IGF-II post administration of MEDI-573 in plasma were evaluated during treatment.
Time Frame
Baseline (Cycle1 Day1 pre-dose), end of treatment (EOT), and 60 days post last dose (Approximately 8 years)
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.
Time Frame
Pre-infusion on Day 1 of each cycle, End of Treatment, Day 30, 60 and 90 post treatment (approximately 8 years)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically-confirmed MBC not deemed amenable to curative surgery or curative radiation therapy
Tumors are positive for ER, PgR, or both
Tumors must be negative for HER2 (by FISH, CISH or IHC)
Female gender and age ≥ 18 years at time of study entry
Postmenopausal
Karnofsky Performance Status ≥ 70
Life expectancy of ≥ 6 months
Exclusion Criteria:
Subjects who received prior chemotherapy, hormonal therapy, immunotherapy or biologic therapy for advanced or metastatic disease with the following exceptions:
Prior adjuvant therapy with an AI and/or tamoxifen is allowed, provided treatment ended at least 2 weeks prior to the first dose of MEDI-573
Prior neoadjuvant and/or adjuvant chemotherapy for breast cancer is allowed
Extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor, or disease that is considered by the investigator to be rapidly progressing or life threatening (eg, subjects who are intended for chemotherapy)
Active brain metastases with the exception of subject has been treated and are asymptomatic and there has been no evidence of CNS progression for at least 4 weeks of first dose of MEDI-573
Evidence of ongoing spinal cord compression or leptomeningeal carcinomatosis
Unresolved toxicities from prior therapy with the exception of alopecia that have not resolved to ≤ Grade 1 at the time of starting study treatment
Previous treatment with agents that target the IGF receptor
History of allergy or reaction attributed to compounds of chemical or biologic composition similar to those of MEDI-573 or AI
History of another invasive malignancy within 5 years except for curatively resected nonmelanoma skin cancer or carcinoma in situ of the cervix
Poorly controlled diabetes mellitus
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MedImmune LLC
Organizational Affiliation
MedImmune LLC
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Research Site
City
Bakersfield
State/Province
California
ZIP/Postal Code
93309
Country
United States
Facility Name
Research Site
City
Pleasant Hill
State/Province
California
ZIP/Postal Code
94523
Country
United States
Facility Name
Research Site
City
Stamford
State/Province
Connecticut
ZIP/Postal Code
06904
Country
United States
Facility Name
Research Site
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
Research Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
Research Site
City
Port Saint Lucie
State/Province
Florida
ZIP/Postal Code
34952-7596
Country
United States
Facility Name
Research Site
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33705
Country
United States
Facility Name
Research Site
City
Athens
State/Province
Georgia
ZIP/Postal Code
30607
Country
United States
Facility Name
Research Site
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30901
Country
United States
Facility Name
Research Site
City
Lawrenceville
State/Province
Georgia
ZIP/Postal Code
30046
Country
United States
Facility Name
Research Site
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
Research Site
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Research Site
City
Frederick
State/Province
Maryland
ZIP/Postal Code
21701
Country
United States
Facility Name
Research Site
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States
Facility Name
Research Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48106-0995
Country
United States
Facility Name
Research Site
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48910
Country
United States
Facility Name
Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55904
Country
United States
Facility Name
Research Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Research Site
City
Lake Success
State/Province
New York
ZIP/Postal Code
11041
Country
United States
Facility Name
Research Site
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Research Site
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Research Site
City
Middletown
State/Province
Ohio
ZIP/Postal Code
45042
Country
United States
Facility Name
Research Site
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43608
Country
United States
Facility Name
Research Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37205
Country
United States
Facility Name
Research Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Research Site
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79410
Country
United States
Facility Name
Research Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23230
Country
United States
Facility Name
Research Site
City
Nassau
ZIP/Postal Code
13932
Country
Bahamas
Facility Name
Research Site
City
Aalst
ZIP/Postal Code
9300
Country
Belgium
Facility Name
Research Site
City
Brasschaat
ZIP/Postal Code
2930
Country
Belgium
Facility Name
Research Site
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
Research Site
City
Bruxelles
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Research Site
City
Edegem
ZIP/Postal Code
2650
Country
Belgium
Facility Name
Research Site
City
Leuven
ZIP/Postal Code
8500
Country
Belgium
Facility Name
Research Site
City
Mons
ZIP/Postal Code
7000
Country
Belgium
Facility Name
Research Site
City
Oshawa
State/Province
Ontario
ZIP/Postal Code
L1G 2B9
Country
Canada
Facility Name
Research Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Research Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
Research Site
City
Le Mans
ZIP/Postal Code
72000
Country
France
Facility Name
Research Site
City
Montpellier
ZIP/Postal Code
34298
Country
France
Facility Name
Research Site
City
Dortmund
ZIP/Postal Code
44137
Country
Germany
Facility Name
Research Site
City
Frankfurt
ZIP/Postal Code
60389
Country
Germany
Facility Name
Research Site
City
Muenchen
ZIP/Postal Code
81657
Country
Germany
Facility Name
Research Site
City
Witten
ZIP/Postal Code
58452
Country
Germany
Facility Name
Research Site
City
Miskolc
ZIP/Postal Code
3526
Country
Hungary
Facility Name
Research Site
City
Nyíregyháza
ZIP/Postal Code
4400
Country
Hungary
Facility Name
Research Site
City
Haifa
ZIP/Postal Code
34362
Country
Israel
Facility Name
Research Site
City
Petach Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Research Site
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Research Site
City
Rechovot
ZIP/Postal Code
76100
Country
Israel
Facility Name
Research Site
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel
Facility Name
Research Site
City
Zerifin
ZIP/Postal Code
70300
Country
Israel
Facility Name
Research Site
City
Lodz
ZIP/Postal Code
90-242
Country
Poland
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08908
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
8036
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28025
Country
Spain
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
Research Site
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Research Site
City
Cardiff.
ZIP/Postal Code
CF14 2TL
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
W1G 6AD
Country
United Kingdom
Facility Name
Research Site
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
Research Site
City
Stoke-on-Trent
ZIP/Postal Code
ST4 6QG
Country
United Kingdom
Facility Name
Research Site
City
Wolverhampton
ZIP/Postal Code
WV10 0QP
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=50&filename=CD-ON-MEDI-573-1030-Protocol_amendment%203_redaction-PDF-A.pdf
Description
CD-ON-MEDI-573-1030-Protocol_amendment 3_redaction-PDF-A
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=50&filename=CD-ON-MEDI-573-1030-SAP-V1_and_V2_Final_Redacted_PDF-A.pdf
Description
CD-ON-MEDI-573-1030-SAP-V1_and_V2_Final_Redacted_PDF-A
Learn more about this trial
Study of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer
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