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.
Brief Title
Study of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer
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).
Categories
Completion Date
Completion Date Type
Actual
Conditions
Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer
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
* 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
Inclusion 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
* 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
Gender
Female
Gender Based
false
Keywords
MEDI-573, breast cancer, metastatic, aromatase inhibitor, anti-IGF
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
99 Years
Minimum Age
18 Years
NCT Id
NCT01446159
Org Class
Industry
Org Full Name
MedImmune LLC
Org Study Id
CD-ON-MEDI-573-1030
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome 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).
Outcome Measure
Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Outcome 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)
Outcome 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.
Outcome Measure
Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
Outcome Time Frame
Up to Day 21 of Cycle 1
Outcome 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.
Outcome Measure
Phase 1b: Number of DLTs
Outcome Time Frame
Up to Day 21 of Cycle 1
Outcome 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.
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.
Outcome Measure
Phase 2: Progression-free Survival (PFS)
Outcome Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Secondary Outcomes
Outcome 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).
Outcome 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)
Outcome Measure
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs
Outcome 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).
Outcome 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)
Outcome Measure
Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs
Outcome 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).
Outcome 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)
Outcome Measure
Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs
Outcome 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.
Outcome Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Outcome Measure
Phase 2: Number of Participants With Best Overall Tumor Response
Outcome 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.
Outcome Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Outcome Measure
Phase 2: Objective Response Rate (ORR)
Outcome 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.
Outcome Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Outcome Measure
Phase 2: Time to Response
Outcome 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.
Outcome Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Outcome Measure
Phase 2: Duration of Response (DR)
Outcome 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.
Outcome Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Outcome Measure
Phase 2: Time to Progression (TTP)
Outcome Description
Overall survival (OS) was measured from treatment start until death.
Outcome Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Outcome Measure
Phase 2: Overall Survival (OS)
Outcome Description
Mean change in tumor size is reported.
Outcome Time Frame
From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Outcome Measure
Phase 2: Change in Tumor Size
Outcome Description
AUC0-day21 of MEDI-573 for Cycle 1 is reported.
Outcome Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Outcome Measure
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
Outcome Description
AUC0-info of MEDI-573 for Cycle 1 is reported.
Outcome Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Outcome Measure
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
Outcome Description
DN AUC0-inf of MEDI-573 for Cycle 1 is reported.
Outcome Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Outcome Measure
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
Outcome Description
Cmax of MEDI-573 for Cycle 1 is reported.
Outcome Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Outcome Measure
Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1
Outcome Description
Tmax of MEDI-573 for Cycle 1 is reported.
Outcome Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Outcome Measure
Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1
Outcome 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).
Outcome Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Outcome Measure
Phase 1b and Phase 2: Systemic Clearance (CL) of MEDI-573 for Cycle 1
Outcome 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.
Outcome Time Frame
Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
Outcome Measure
Phase 1b and Phase 2: Terminal Half Life (t1/2) of MEDI-573 for Cycle 1
Outcome Description
The mean concentration profiles of both IGF-I and IGF-II post administration of MEDI-573 in plasma were evaluated during treatment.
Outcome Time Frame
Baseline (Cycle1 Day1 pre-dose), end of treatment (EOT), and 60 days post last dose (Approximately 8 years)
Outcome Measure
Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II
Outcome Description
Participants With Positive ADA to MEDI-573 are reported.
Outcome Time Frame
Pre-infusion on Day 1 of each cycle, End of Treatment, Day 30, 60 and 90 post treatment (approximately 8 years)
Outcome Measure
Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
99
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Joseph Sparano
Investigator Email
jsparano@montefiore.org
Investigator Phone
718-405-8404