A study in women with advanced breast cancer treated with standard therapy with or without MEDI-573

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2011-000198-29-HU
• Date of registration: 11/08/2011
• Prospective Registration: Yes
• Primary sponsor: MedImmune, LLC
• Public title: A study in women with advanced breast cancer treated with standard therapy with or without MEDI-573
• Scientific 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)
• Date of first enrolment: 12/10/2011
• Target sample size: 178
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000198-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, France, Germany, Hungary, Israel, Poland, Spain, United Kingdom, United States

Contacts

• Name: Information Center
• Affiliation: MedImmune

• Name: Information Center
• Affiliation: MedImmune

Key inclusion & exclusion criteria

Inclusion criteria:
Histologically-confirmed MBC not deemed amenable to curative surgery or curative radiation therapy
Tumors are pisitive for ER, PgR, or both
Tumors must be negative for HER2 (by FISH or CISH)
Female gender and age = 18 years at time of study entry
Postmenopausal
Karnofsky Performance Status = 70
Life expectancy of = 6 months

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 18

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 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 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Advanced Metastatic Breast Cancer (MBC)
MedDRA version: 14.1 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10006202 Term: Breast cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: MEDI-573
Product Code: MEDI-573
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: N/A
CAS Number: 1204390-13-5
Current Sponsor code: MEDI-573
Other descriptive name: AZD4253, MABABXLONAZ2.1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: not less then
Concentration number: 22.5-

Primary Outcome(s)

Secondary Objective: Six secondary objectives

• To describe the safety and tolerability of MEDI-573 when used in combination with an AI

• To evaluate the anti-tumor activity of MEDI-573 when used in combination with an AI versus treatment with an AI alone

• To evaluate overall survival (OS) in subjects treated with MEDI-573 when used in combination with an AI versus treatment with an AI alone

• To describe the pharmacokinetics (PK) of MEDI-573 when used in combination with an AI

• To evaluate the pharmacodynamics of MEDI-573 when used in combination with an AI on circulating levels of insulin-like growth factor I (IGF-I) and insulin-like growth factor II (IGF-II)

• To evaluate the immunogenicity (IM) of MEDI-573 when used in combination with an AI

Main Objective: Primary objective of the dose-evaluation phase (Phase 1) is to evaluate the safety and tolerability of 3 dose levels of MEDI 573 in combination with an AI in subjects with hormone receptor positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative MBC.

The primary objective of the randomization phase (Phase 2) is to evaluate the progression-free survival (PFS) of subjects with HR+, HER2-negative MBC treated with MEDI-573 and an AI versus treatment with an AI alone.

Primary end point(s): Phase 1b (dose-evaluation Phase)
The primary endpoints for safety are the number of subjects with a DLT as well as the adverse events (AEs) and serious adverse events (SAEs) occurring during the protocol-specified period.

Phase 2 (Randomization Phase)
The primary endpoint is PFS, measured from randomization until the documentation of disease progression (according to Response Evaluation Criteria in Solid Tumors, Version 1.1) or death due to any cause, whichever occurs first.

Timepoint(s) of evaluation of this end point: After the first cycle (3 weeks) subjects will be evaluated every 9 weeks for safety and for disease progression

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Timepoint(s) of evaluation for Safety and Tolerability of MEDI-573 in Phase 2: Multiple safety visits during the first cycle, then every 9 weeks until disease progression.

Timepoints for evaluation for the Pharmacokinetic, Pharmacodynamic and Immunogenicity endpoints: Multiple timepoints during the first cycle, then every 9 weeks during treatment.

Timepoints for evaluation for Efficacy endpoints: Subjects will be evaluated for tumor response or progression at regular 9-week intervals until progression of disease. After disease progression, subjects will be followed for overall survival every 12 weeks until death or until the end of the study.

Secondary end point(s): Efficacy
Endpoints include objective response rate, time to response, duration of response, time to progression, OS, and change in tumor size. Response Evaluation Criteria in Solid Tumors (version 1.1) guidelines will be used to evaluate tumor response.

Safety
The safety endpoints include AEs, SAEs, and changes in clinical laboratory evaluations from baseline.

Secondary ID(s)

2011-000198-29-ES

CD-ON-MEDI-573-1030

NCT01446159

Source(s) of Monetary Support

MedImmune, LLC

Ethics review

Status: Approved
Approval date:
Contact: