A Phase 2 interventional study of MEDI-573 and Aromatase Inhibitor in Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer, sponsored by MedImmune LLC. Completed at 71 sites in 11 countries. Open to female participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2020-06-02.
Sponsored by MedImmune LLC (part of AstraZeneca) · Phase 2, Interventional, and Treatment
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.
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).
14,825 studies on the registry are indexed under Breast Neoplasms; 3,319 are open to participants now.
This study's enrollment of 188 is above the median of 72 across 10,896 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →MedImmune LLC is the lead sponsor of 270 studies on the registry; none are open to participants now.
Of its 52 completed or terminated interventional studies of FDA-regulated products, 29 (56%) have results posted.
First submitted after MedImmune LLC became part of AstraZeneca.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Subjects who received prior chemotherapy, hormonal therapy, immunotherapy or biologic therapy for advanced or disease with the following exceptions:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: MEDI-573 · Drug: Aromatase Inhibitor
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.
Drug: MEDI-573 · Drug: Aromatase Inhibitor
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.
Drug: MEDI-573 · Drug: Aromatase Inhibitor
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.
Drug: Aromatase Inhibitor
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.
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.
This study also gives Anastrozole, Exemestane. No intervention listed here names it: that was found by reading the record.
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).
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)
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.
Time frame: Up to Day 21 of Cycle 1
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.
Time frame: Up to Day 21 of Cycle 1
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.
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
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).
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)
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).
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)
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).
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)
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.
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
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.
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
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.
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
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.
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
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.
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Phase 2: Overall Survival (OS)
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)
Phase 2: Change in Tumor Size
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)
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.
Time frame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
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.
Time frame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
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.
Time frame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
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.
Time frame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
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.
Time frame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
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).
Time frame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
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.
Time frame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
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.
Time frame: Baseline (Cycle1 Day1 pre-dose), end of treatment (EOT), and 60 days post last dose (Approximately 8 years)
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.
Time frame: Pre-infusion on Day 1 of each cycle, End of Treatment, Day 30, 60 and 90 post treatment (approximately 8 years)
The study was conducted across 10 countries (Belgium, Canada, France, Germany, Hungary, Israel, Spain, Poland, United Kingdom, USA).
| Milestone | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|---|---|
| Started | 3 | 3 | 92 | 85 |
| Completed | 0 | 0 | 21 | 23 |
| Not completed | 3 | 3 | 71 | 62 |
| Withdrew: Withdrawal by subject | 1 | 0 | 14 | 11 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 | 2 |
| Withdrew: Death | 2 | 3 | 43 | 36 |
| Withdrew: Other | 0 | 0 | 13 | 13 |
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).
| Participants | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|---|---|
| Any TEAEs | 3 | 3 | 90 | 82 |
| Any TESAEs | 2 | 0 | 21 | 16 |
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.
| Participants | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI |
|---|---|---|---|
| Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) | 0 | 0 | 0 |
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.
| DLT events | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI |
|---|---|---|---|
| Phase 1b: Number of DLTs | 0 | 0 | 0 |
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.
| Months | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|
| Phase 2: Progression-free Survival (PFS) | 12.65 (8.15 to 15.54) | 11.33 (8.54 to 15.54) |
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).
| Participants | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|---|---|
| Anemia | 1 | 1 | 17 | 10 |
| Eosinophilia | 0 | 0 | 1 | 0 |
| Leukopenia | 0 | 0 | 0 | 3 |
| Lymphopenia | 0 | 0 | 1 | 2 |
| Neutropenia | 1 | 1 | 3 | 4 |
| Pancytopenia | 0 | 0 | 0 | 1 |
| Thrombocytopenia | 0 | 2 | 1 | 3 |
| Granulocyte count decreased | 0 | 1 | 0 | 0 |
| Hemoglobin decreased | 0 | 1 | 1 | 0 |
| Lymphocyte count decreased | 0 | 0 | 2 | 1 |
| Monocyte count decreased | 0 | 0 | 1 | 0 |
| Neutrophil count decreased | 0 | 0 | 2 | 0 |
| Neutrophil count increased | 0 | 0 | 1 | 0 |
| Platelet count decreased | 0 | 0 | 4 | 1 |
| White blood cell count decreased | 0 | 0 | 2 | 1 |
| Alanine aminotransferase increased | 2 | 0 | 8 | 4 |
| Aspartate aminotransferase increased | 2 | 1 | 6 | 4 |
| Blood albumin decreased | 0 | 0 | 1 | 0 |
| Blood albumin increased | 0 | 1 | 0 | 0 |
| Blood alkaline phosphatase increased | 0 | 1 | 5 | 5 |
| Blood bicarbonate decreased | 0 | 0 | 1 | 0 |
| Blood bilirubin increased | 0 | 0 | 0 | 1 |
| Blood chloride decreased | 0 | 0 | 1 | 0 |
| Blood creatine increased | 0 | 1 | 1 | 0 |
| Blood creatinine decreased | 0 | 0 | 0 | 1 |
| Blood creatinine increased | 0 | 1 | 8 | 2 |
| Blood glucose increased | 0 | 0 | 1 | 1 |
| Blood lactate dehydrogenase increased | 0 | 0 | 1 | 1 |
| Blood magnesium decreased | 0 | 1 | 0 | 0 |
| Blood potassium decreased | 0 | 0 | 1 | 0 |
| Blood sodium decreased | 0 | 1 | 0 | 0 |
| Blood triglycerides increased | 0 | 0 | 1 | 2 |
| Blood urea increased | 0 | 0 | 1 | 0 |
| Blood uric acid increased | 0 | 0 | 3 | 1 |
| Gamma-glutamyl transferase decreased | 0 | 1 | 0 | 0 |
| Gamma-glutamyl transferase increased | 1 | 1 | 9 | 4 |
| Protein total decreased | 0 | 1 | 0 | 1 |
| Leukocytosis | 0 | 0 | 0 | 1 |
| Neutrophilia | 0 | 0 | 1 | 0 |
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).
| Participants | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|---|---|
| Bradycardia | 1 | 0 | 1 | 1 |
| Palpitations | 1 | 0 | 1 | 2 |
| Pyrexia | 0 | 0 | 10 | 6 |
| Temperature intolerance | 0 | 0 | 1 | 1 |
| Body temperature increased | 0 | 0 | 1 | 0 |
| Aspiration | 0 | 0 | 1 | 0 |
| Dyspnoea | 2 | 0 | 18 | 14 |
| Hypertension | 0 | 0 | 8 | 13 |
| Hypotension | 1 | 0 | 1 | 0 |
| Orthostatic hypotension | 0 | 0 | 1 | 0 |
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).
| Participants | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|---|---|
| Sinus bradycardia | 1 | 0 | 2 | 0 |
| Sinus tachycardia | 0 | 0 | 0 | 1 |
| Supraventricular tachycardia | 0 | 0 | 0 | 2 |
| Tachycardia | 0 | 0 | 1 | 2 |
| Angina pectoris | 0 | 0 | 0 | 1 |
| Arrhythmia | 0 | 0 | 0 | 1 |
| Atrial fibrillation | 0 | 0 | 1 | 2 |
| Atrial flutter | 0 | 0 | 0 | 1 |
| Atrioventricular block first degree | 0 | 0 | 1 | 0 |
| Bradycardia | 1 | 0 | 1 | 1 |
| Cardiac failure | 0 | 0 | 1 | 0 |
| Cardiac valve disease | 0 | 0 | 1 | 0 |
| Palpitation | 1 | 0 | 1 | 2 |
| Ventricular extrasystoles | 0 | 0 | 1 | 0 |
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.
| Participants | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|
| CR | 1 | 2 |
| PR | 23 | 21 |
| SD | 48 | 46 |
| PD | 15 | 12 |
| NE | 2 | 4 |
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.
| Percentage of participants | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|
| Phase 2: Objective Response Rate (ORR) | 27.0 (18.1 to 37.4) | 27.1 (18.0 to 37.8) |
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.
| Months | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|
| Phase 2: Time to Response | 4.22 (1.7 to 18.0) | 3.98 (1.9 to 16.8) |
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.
| Months | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|
| Phase 2: Duration of Response (DR) | 14.55 (4.5 to 58.8) | 17.18 (2.1 to 45.1) |
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.
| Months | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|
| Phase 2: Time to Progression (TTP) | 14.39 (8.34 to 18.69) | 11.33 (8.54 to 17.97) |
Overall survival (OS) was measured from treatment start until death.
| Months | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|
| Phase 2: Overall Survival (OS) | 39.39 (0.3 to 73.2) | 38.34 (0.3 to 51.6) |
Mean change in tumor size is reported.
| Centimeters | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|
| Phase 2: Change in Tumor Size | -36.2 ± 35.8 | -26.8 ± 37.2 |
AUC0-day21 of MEDI-573 for Cycle 1 is reported.
| μg·day/mL | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI |
|---|---|---|---|
| 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 | 1430 ± 867 | 4500 ± 725 | 7990 ± 1590 |
AUC0-info of MEDI-573 for Cycle 1 is reported.
| μg·day/mL | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI |
|---|---|---|---|
| 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 | 1500 ± 955 | 4930 ± 691 | 9570 ± 2310 |
DN AUC0-inf of MEDI-573 for Cycle 1 is reported.
| day·kg·μg/mL/mg | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI |
|---|---|---|---|
| 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 | 150 ± 95.5 | 164 ± 23.0 | 213 ± 51.3 |
Cmax of MEDI-573 for Cycle 1 is reported.
| μg/mL | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI |
|---|---|---|---|
| Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1 | 269 ± 74.1 | 624 ± 210 | 1070 ± 253 |
Tmax of MEDI-573 for Cycle 1 is reported.
| Day | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI |
|---|---|---|---|
| Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1 | 0.04 (0 to 0.09) | 0.07 (0.06 to 0.08) | 0.07 (0.03 to 0.17) |
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).
| mL/day/kg | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI |
|---|---|---|---|
| Phase 1b and Phase 2: Systemic Clearance (CL) of MEDI-573 for Cycle 1 | 8.29 ± 3.86 | 6.17 ± 0.889 | 4.96 ± 1.13 |
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.
| Day | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI |
|---|---|---|---|
| Phase 1b and Phase 2: Terminal Half Life (t1/2) of MEDI-573 for Cycle 1 | 4.38 ± 1.07 | 5.91 ± 2.09 | 8.45 ± 2.23 |
The mean concentration profiles of both IGF-I and IGF-II post administration of MEDI-573 in plasma were evaluated during treatment.
| ng/mL | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|---|---|
| Baseline: Free IGF-I Concentration | 2.57 ± 0.712 | 1.25 ± 0.635 | 3.49 ± 4.39 | 1.89 ± 1.24 |
| Baseline: Free IGF-II Concentration | 3.81 ± 1.66 | 3.07 ± 0.709 | 3.01 ± 1.20 | 3.03 ± 1.12 |
| EOT: Free IGF-I Concentration | 0.724 ± 0.421 | 0.313 ± 0.0 | 0.346 ± 0.130 | 2.32 ± 3.64 |
| EOT: Free IGF-II Concentration | 0.625 ± 0.0 | 0.625 ± 0.0 | 0.641 ± 0.102 | 3.12 ± 1.22 |
| 60 days post last dose: Free IGF-I Concentration | 1.54 ± NA | 1.33 ± 0.3 | 1.02 ± 1.29 | 4.62 ± 8.52 |
| 60 days post last dose: Free IGF-II Concentration | 1.49 ± NA | 0.625 ± 0.0 | 0.984 ± 0.734 | 3.38 ± 1.51 |
Participants With Positive ADA to MEDI-573 are reported.
| Participants | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI |
|---|---|---|---|
| Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573 | 0 | 0 | 1 |
Collected over 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). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | 2/6 (33.3%) | 2/3 (66.7%) | 3/3 (100%) |
| MEDI-573 30 mg/kg + AI | 3/6 (50%) | 0/3 (0%) | 3/3 (100%) |
| MEDI-573 45 mg/kg + AI | 43/184 (23.4%) | 21/92 (22.8%) | 86/92 (93.5%) |
| Aromatase Inhibitor | 36/170 (21.2%) | 16/85 (18.8%) | 79/85 (92.9%) |
| Event | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 1/3 | 0/3 | 0/92 | 0/85 |
| Chest painGeneral disorders | 1/3 | 0/3 | 0/92 | 0/85 |
| Sinus bradycardiaCardiac disorders | 1/3 | 0/3 | 0/92 | 0/85 |
| Uterine cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/3 | 0/3 | 0/92 | 0/85 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 1/3 | 0/3 | 0/92 | 2/85 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 1/3 | 0/3 | 0/92 | 0/85 |
| HypotensionVascular disorders | 1/3 | 0/3 | 0/92 | 0/85 |
| VomitingGastrointestinal disorders | 0/3 | 0/3 | 3/92 | 0/85 |
| Supraventricular tachycardiaCardiac disorders | 0/3 | 0/3 | 0/92 | 2/85 |
| Atrial flutterCardiac disorders | 0/3 | 0/3 | 0/92 | 1/85 |
| Event | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor |
|---|---|---|---|---|
| FatigueGeneral disorders | 2/3 | 3/3 | 41/92 | 27/85 |
| Weight decreasedInvestigations | 0/3 | 2/3 | 6/92 | 5/85 |
| HypocalcaemiaMetabolism and nutrition disorders | 2/3 | 0/3 | 7/92 | 1/85 |
| Musculoskeletal chest painMusculoskeletal and connective tissue disorders | 2/3 | 1/3 | 12/92 | 11/85 |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/3 | 2/3 | 1/92 | 3/85 |
| ConstipationGastrointestinal disorders | 2/3 | 1/3 | 21/92 | 23/85 |
| NauseaGastrointestinal disorders | 1/3 | 2/3 | 34/92 | 30/85 |
| Alanine aminotransferase increasedInvestigations | 2/3 | 0/3 | 8/92 | 4/85 |
| Aspartate aminotransferase increasedInvestigations | 2/3 | 1/3 | 6/92 | 4/85 |
| HyponatraemiaMetabolism and nutrition disorders | 2/3 | 0/3 | 3/92 | 4/85 |
Intent-to-Treat (ITT) population included all participants who received any study therapy and were analysed per their randomized treatment group.
| Age, Continuous(Years) | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor | Total |
|---|---|---|---|---|---|
| Mean | 66.3 ± 12.3 | 61.0 ± 8.7 | 63.2 ± 10.5 | 63.3 ± 11.0 | 63.2 ± 10.7 |
| Sex: Female, Male(Participants) | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor | Total |
|---|---|---|---|---|---|
| Female | 3 | 3 | 92 | 85 | 183 |
| Male | 0 | 0 | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 7 | 6 | 13 |
| Not Hispanic or Latino | 3 | 3 | 85 | 79 | 170 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | MEDI-573 10 mg/kg + Aromatase Inhibitor (AI) | MEDI-573 30 mg/kg + AI | MEDI-573 45 mg/kg + AI | Aromatase Inhibitor | Total |
|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 6 | 1 | 8 |
| White | 2 | 3 | 84 | 82 | 171 |
| More than one race | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 2 | 1 | 3 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Jun 2011 to primary completion in Jun 2019, 96 months.
Of 232 industry-sponsored phase 2 interventional studies under Breast Neoplasms, half reached primary completion within 34 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 53. This study's 96 months is above that.
Counting every sponsor, half of 1,302 studies reached it within 51 months; a quarter within 30 and three quarters within 82.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in May 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Aromatase inhibitors