Hormone-sensitive, HER-2 Negative Metastatic Breast CancerPhase 2NCT01446159
Study of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer
A Phase 2 study testing MEDI-573 and Aromatase Inhibitor in people with Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer, run by MedImmune LLC at 71 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years, women only
- Conditions the study is for
- Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer
- What is being tested?
- MEDI-573 and Aromatase Inhibitor
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 188 participants
- Where
- 71 sitesin 11 countries
- Study dates
- 13 Jun 2011to 28 Jun 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
71 sites in 11 countries.
71 sites in 11 countries
United States34 sites
Research Site
Albuquerque, New Mexico, 87131
Research Site
Ann Arbor, Michigan, 48106-0995
Research Site
Athens, Georgia, 30607
Research Site
Augusta, Georgia, 30901
Research Site
Bakersfield, California, 93309
Research Site
Baltimore, Maryland, 21224
Research Site
Baltimore, Maryland, 21231
Research Site
Bethesda, Maryland, 20817
Research Site
Canton, Ohio, 44718
Research Site
Cincinnati, Ohio, 45267
Research Site
Cleveland, Ohio, 44106
Research Site
Cleveland, Ohio, 44195
Research Site
Fort Myers, Florida, 33901
Research Site
Frederick, Maryland, 21701
Research Site
Houston, Texas, 77030
Research Site
Lake Success, New York, 11041
Research Site
Lake Success, New York, 11042
Research Site
Lansing, Michigan, 48910
Research Site
Lawrenceville, Georgia, 30046
Research Site
Lubbock, Texas, 79410
Research Site
Memphis, Tennessee, 38120
Research Site
Middletown, Ohio, 45042
Research Site
Nashville, Tennessee, 37205
Research Site
Orlando, Florida, 32804
Research Site
Pleasant Hill, California, 94523
Research Site
Port Saint Lucie, Florida, 34952-7596
Research Site
Richmond, Virginia, 23230
Research Site
Rochester, Minnesota, 55904
Research Site
Rockville, Maryland, 20850
Research Site
Scarborough, Maine, 04074
Research Site
Scottsdale, Arizona, 85259
Research Site
St. Petersburg, Florida, 33705
Research Site
Stamford, Connecticut, 06904
Research Site
Toledo, Ohio, 43608
Belgium7 sites
Research Site
Aalst, 9300
Research Site
Brasschaat, 2930
Research Site
Bruges, 8000
Research Site
Brussels, 1000
Research Site
Edegem, 2650
Research Site
Leuven, 8500
Research Site
Mons, 7000
Israel6 sites
Research Site
Haifa, 34362
Research Site
Petah Tikva, 49100
Research Site
Ramat Gan, 52621
Research Site
Rehovot, 76100
Research Site
Tel Aviv, 64239
Research Site
Tsrifin, 70300
Spain6 sites
Research Site
Barcelona, 08041
Research Site
Barcelona, 08908
Research Site
Barcelona, 8036
Research Site
Madrid, 28025
Research Site
Madrid, 28034
Research Site
Málaga, 29010
United Kingdom5 sites
Research Site
Cardiff, CF14 2TL
Research Site
London, W1G 6AD
Research Site
Southampton, SO16 6YD
Research Site
Stoke-on-Trent, ST4 6QG
Research Site
Wolverhampton, WV10 0QP
Germany4 sites
Research Site
Dortmund, 44137
Research Site
Frankfurt, 60389
Research Site
München, 81657
Research Site
Witten, 58452
Canada3 sites
Research Site
Montreal, Quebec, H2L 4M1
Research Site
Oshawa, Ontario, L1G 2B9
Research Site
Ottawa, Ontario, K1H 8L6
The Bahamas1 site
Research Site
Nassau, 13932
About this study
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 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.
Read the 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).
- Being tested
- MEDI-573, Aromatase Inhibitor
- Keywords
- MEDI-573, breast cancer, metastatic, aromatase inhibitor, anti-IGF
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MEDI-573Drug
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 InhibitorDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| MEDI-573 10 mg/kg + AI | Experimental | 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. Receives: Drug: MEDI-573; Drug: Aromatase Inhibitor |
| MEDI-573 30 mg/kg + AI | Experimental | 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. Receives: Drug: MEDI-573; Drug: Aromatase Inhibitor |
| MEDI-573 45 mg/kg + AI | Experimental | 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. Receives: Drug: MEDI-573; Drug: Aromatase Inhibitor |
| Aromatase Inhibitor | Experimental | 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. Receives: Drug: Aromatase Inhibitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Secondary outcomes (19)
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).
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Pre-infusion on Day 1 of each cycle, End of Treatment, Day 30, 60 and 90 post treatment (approximately 8 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2011 (estimated)
- Study start13 Jun 2011
- Primary completion28 Jun 2019
- Study completion28 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hormone-sensitive, HER-2 Negative Metastatic Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 188 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedImmune LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MedImmune LLC, Study director, MedImmune LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01446159
- Sponsor's protocol ID
- CD-ON-MEDI-573-1030
- Status last verified
- May 2020
- First submitted
- 12 Sep 2011
- Last updated
- 2 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01446159
- Acronym / sponsor ID
- CD-ON-MEDI-573-1030
- Keywords
- MEDI-573, breast cancer, metastatic, aromatase inhibitor, anti-IGF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 188 participants (actual)
- Lead sponsor
- MedImmune LLCIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2011 (actual)
- Primary completion
- 28 Jun 2019 (actual)
- Study completion
- 28 Jun 2019 (actual)
- First posted
- 5 Oct 2011 (estimated)
- Results
- Posted 28 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MEDI-573 10 mg/kg + AI | Experimental | Drug: MEDI-573, Drug: Aromatase InhibitorParticipants 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. |
| MEDI-573 30 mg/kg + AI | Experimental | Drug: MEDI-573, Drug: Aromatase InhibitorParticipants 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. |
| MEDI-573 45 mg/kg + AI | Experimental | Drug: MEDI-573, Drug: Aromatase InhibitorParticipants 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. |
| Aromatase Inhibitor | Experimental | Drug: Aromatase InhibitorParticipants 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. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (11 listed)
- Subjects who received prior chemotherapy, hormonal therapy, immunotherapy or biologic therapy for advanced or metastatic disease with the following exceptions:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MEDI-573Intravenous 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. | Drug | MEDI-573 10 mg/kg + AI, MEDI-573 30 mg/kg + AI, MEDI-573 45 mg/kg + AI |
| Aromatase InhibitorAromatase 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. | Drug | Aromatase Inhibitor, MEDI-573 10 mg/kg + AI, MEDI-573 30 mg/kg + AI, MEDI-573 45 mg/kg + AI |
Primary outcome
Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
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)
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)
Time frame: Up to Day 21 of Cycle 1
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
Time frame: Up to Day 21 of Cycle 1
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)
Time frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
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.
19 secondary outcomes
Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs
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
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
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
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)
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 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)
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 frame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Phase 2: Overall Survival (OS)
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
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
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
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
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
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
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
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
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
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
Time frame: Pre-infusion on Day 1 of each cycle, End of Treatment, Day 30, 60 and 90 post treatment (approximately 8 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- CD-ON-MEDI-573-1030-Protocol\_amendment 3\_redaction-PDF-ALink provided by the sponsor.
- CD-ON-MEDI-573-1030-SAP-V1\_and\_V2\_Final\_Redacted\_PDF-ALink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MedImmune LLC study director
MedImmune LLC
71 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MEDI-573 and Aromatase Inhibitor in people with Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer, run by MedImmune LLC at 71 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 71 sites in United States, Belgium, Israel, Spain, United Kingdom and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) (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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2020.