Study of MEDI-573 Plus Standard Endocrine Therapy for Women With Hormone-sensitive Metastatic Breast Cancer

NCT01446159 | Completed Phase 2 Results DMC

• 1 other identifier: CD-ON-MEDI-573-1030
• Study Type: interventional
• Target: 188
• Locations: 11 countries
• Sites: 71

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.

Conditions

Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer

Keywords

MEDI-573, breast cancer, metastatic, aromatase inhibitor, anti-IGF

Outcome Measures

Primary Outcomes (4)

• 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).

  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.

  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.

  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.

  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

  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

  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

  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

  From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)

• Phase 2: Objective Response Rate (ORR)

  From Day 1 until disease progression or death due to any cause, whichever occurred first (Approximately 8 years)

Study Arms (4)

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.

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.

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.

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.

Drug: Aromatase Inhibitor

Interventions

MEDI-573 DRUG

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.

MEDI-573 10 mg/kg + AI; MEDI-573 30 mg/kg + AI; MEDI-573 45 mg/kg + AI

Aromatase Inhibitor DRUG

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.

Aromatase Inhibitor; MEDI-573 10 mg/kg + AI; MEDI-573 30 mg/kg + AI; MEDI-573 45 mg/kg + AI

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (71)

Research Site

Scottsdale, Arizona, 85259, United States

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Bakersfield, California, 93309, United States

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Pleasant Hill, California, 94523, United States

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Stamford, Connecticut, 06904, United States

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Fort Myers, Florida, 33901, United States

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Orlando, Florida, 32804, United States

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Port Saint Lucie, Florida, 34952-7596, United States

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St. Petersburg, Florida, 33705, United States

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Athens, Georgia, 30607, United States

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Augusta, Georgia, 30901, United States

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Lawrenceville, Georgia, 30046, United States

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Scarborough, Maine, 04074, United States

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Baltimore, Maryland, 21224, United States

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Baltimore, Maryland, 21231, United States

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Bethesda, Maryland, 20817, United States

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Frederick, Maryland, 21701, United States

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Rockville, Maryland, 20850, United States

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Ann Arbor, Michigan, 48106-0995, United States

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Lansing, Michigan, 48910, United States

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Rochester, Minnesota, 55904, United States

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Albuquerque, New Mexico, 87131, United States

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Lake Success, New York, 11041, United States

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Lake Success, New York, 11042, United States

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Canton, Ohio, 44718, United States

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Cincinnati, Ohio, 45267, United States

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Cleveland, Ohio, 44106, United States

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Cleveland, Ohio, 44195, United States

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Middletown, Ohio, 45042, United States

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Toledo, Ohio, 43608, United States

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Memphis, Tennessee, 38120, United States

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Nashville, Tennessee, 37205, United States

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Houston, Texas, 77030, United States

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Lubbock, Texas, 79410, United States

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Richmond, Virginia, 23230, United States

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Aalst, 9300, Belgium

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Brasschaat, 2930, Belgium

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Bruges, 8000, Belgium

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Brussels, 1000, Belgium

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Edegem, 2650, Belgium

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Leuven, 8500, Belgium

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Mons, 7000, Belgium

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Oshawa, Ontario, L1G 2B9, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Le Mans, 72000, France

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Montpellier, 34298, France

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Dortmund, 44137, Germany

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Frankfurt, 60389, Germany

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München, 81657, Germany

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Witten, 58452, Germany

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Miskolc, 3526, Hungary

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Nyíregyháza, 4400, Hungary

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Haifa, 34362, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 52621, Israel

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Rehovot, 76100, Israel

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Tel Aviv, 64239, Israel

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Ẕerifin, 70300, Israel

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Lodz, 90-242, Poland

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Barcelona, 08041, Spain

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Barcelona, 08908, Spain

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Barcelona, 8036, Spain

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Madrid, 28025, Spain

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Madrid, 28034, Spain

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Málaga, 29010, Spain

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Nassau, 13932, The Bahamas

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Cardiff, CF14 2TL, United Kingdom

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London, W1G 6AD, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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Stoke-on-Trent, ST4 6QG, United Kingdom

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Wolverhampton, WV10 0QP, United Kingdom

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Related Links

• CD-ON-MEDI-573-1030-Protocol\_amendment 3\_redaction-PDF-A
• CD-ON-MEDI-573-1030-SAP-V1\_and\_V2\_Final\_Redacted\_PDF-A

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

dusigitumab; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Results Point of Contact

• Title: Shahram Rahimian
• Organization: MedImmune, LLC

information.center@astrazeneca.com

+1-800-236-9933

Study Officials

• MedImmune LLC

  MedImmune LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2011
• First Posted: October 5, 2011
• Study Start: June 13, 2011
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2019
• Last Updated: June 2, 2020
• Results First Posted: August 28, 2018

Record last verified: 2020-05

Locations

ES (6); GB (5); IL (6); US (34); CA (3); FR (2); DE (4); PL (1); BE (7); TH (1); HU (2)