Clinical trial NCT01446159: Study of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer
Official title: A Phase 1b/2 Randomized Study of MEDI-573 in Combination With an Aromatase Inhibitor (AI) Versus AI Alone in Women With Metastatic Breast Cancer (MBC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer
Keywords: MEDI-573, breast cancer, metastatic, aromatase inhibitor, anti-IGF
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2011-10-05
Enrollment: 188
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study to evaluate the safety, tolerability, antitumor activity, and pharmacology of MEDI-573 in combination with an aromatase inhibitor (AI) in adult subjects with HR+, HER2-negative MBC.

Detailed description: This is a Phase 1b/2, multicenter, open-label study to evaluate the safety, tolerability, antitumor activity, and pharmacology of MEDI-573 in combination with an AI in adult subjects with HR+, HER2-negative MBC. This study has 2 phases: a dose-evaluation phase (Phase 1b) and a randomization phase (Phase 2).

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

Primary outcomes:
measure: Phase 1b and Phase 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: 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)
measure: Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: Up to Day 21 of Cycle 1
measure: Phase 1b: Number of DLTs
timeFrame: Up to Day 21 of Cycle 1
measure: Phase 2: Progression-free Survival (PFS)
timeFrame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
Secondary outcomes:
measure: Phase 1b and Phase 2: Number of Participants With Abnormal Clinical Laboratory Results Reported as TEAEs
timeFrame: 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)
measure: Phase 1b and Phase 2: Number of Participants With Abnormal Vital Signs Reported as TEAEs
timeFrame: 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)
measure: Phase 1b and Phase 2: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs
timeFrame: 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)
measure: Phase 2: Number of Participants With Best Overall Tumor Response
timeFrame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
measure: Phase 2: Objective Response Rate (ORR)
timeFrame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
measure: Phase 2: Time to Response
timeFrame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
measure: Phase 2: Duration of Response (DR)
timeFrame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
measure: Phase 2: Time to Progression (TTP)
timeFrame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
measure: Phase 2: Overall Survival (OS)
timeFrame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
measure: Phase 2: Change in Tumor Size
timeFrame: From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)
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
timeFrame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
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
timeFrame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
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
timeFrame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
measure: Phase 1b and Phase 2: Maximum Observed Serum Concentration (Cmax) of MEDI-573 for Cycle 1
timeFrame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
measure: Phase 1b and Phase 2: Time to Reach Maximum Observed Serum Concentration (Tmax) of MEDI-573 for Cycle 1
timeFrame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
measure: Phase 1b and Phase 2: Systemic Clearance (CL) of MEDI-573 for Cycle 1
timeFrame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
measure: Phase 1b and Phase 2: Terminal Half Life (t1/2) of MEDI-573 for Cycle 1
timeFrame: Cycle 1 Days 1, 2, 8, 15, and 21 (Cycle 2 Day 1, pre-dose)
measure: Phase 1b and Phase 2: Concentration of Insulin-like Growth Factor (IGF) I and IGF-II
timeFrame: Baseline (Cycle1 Day1 pre-dose), end of treatment (EOT), and 60 days post last dose (Approximately 8 years)
measure: Phase 1b and Phase 2: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI-573
timeFrame: Pre-infusion on Day 1 of each cycle, End of Treatment, Day 30, 60 and 90 post treatment (approximately 8 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Research Site
state: Arizona
city: Bakersfield
country: United States
facility: Research Site
state: California
city: Pleasant Hill
country: United States
facility: Research Site
state: California
city: Stamford
country: United States
facility: Research Site
state: Connecticut
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Port Saint Lucie
country: United States
facility: Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Research Site
state: Florida
city: Athens
country: United States
facility: Research Site
state: Georgia
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Lawrenceville
country: United States
facility: Research Site
state: Georgia
city: Scarborough
country: United States
facility: Research Site
state: Maine
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Frederick
country: United States
facility: Research Site
state: Maryland
city: Rockville
country: United States
facility: Research Site
state: Maryland
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Lansing
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Albuquerque
country: United States
facility: Research Site
state: New Mexico
city: Lake Success
country: United States
facility: Research Site
state: New York
city: Lake Success
country: United States
facility: Research Site
state: New York
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Middletown
country: United States
facility: Research Site
state: Ohio
city: Toledo
country: United States
facility: Research Site
state: Ohio
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
city: Lubbock
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Nassau
country: Bahamas
facility: Research Site
city: Aalst
country: Belgium
facility: Research Site
city: Brasschaat
country: Belgium
facility: Research Site
city: Brugge
country: Belgium
facility: Research Site
city: Bruxelles
country: Belgium
facility: Research Site
city: Edegem
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Mons
country: Belgium
facility: Research Site
city: Oshawa
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Le Mans
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Dortmund
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Muenchen
country: Germany
facility: Research Site
city: Witten
country: Germany
facility: Research Site
city: Miskolc
country: Hungary
facility: Research Site
city: Nyíregyháza
country: Hungary
facility: Research Site
city: Haifa
country: Israel
facility: Research Site
city: Petach Tikva
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Rechovot
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Zerifin
country: Israel
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Cardiff.
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
city: Stoke-on-Trent
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: MedImmune LLC
name: MedImmune LLC
role: STUDY_DIRECTOR
References: