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

• Register: EUCTR
• Last refreshed on: 10 December 2019
• Main ID: EUCTR2011-000198-29-ES
• Date of registration: 09/08/2011
• 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: 25/10/2011
• Target sample size: 267
• 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: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• 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, Italy, Spain, United Kingdom, United States

Contacts

• Name: Information Center
• Affiliation: MedImmune

• Name: Information Center
• Affiliation: MedImmune

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects must meet the following criteria:
Female gender and age ? 18 years at time of study entry
Women must be postmenopausal
Written informed consent and any locally-required authorization
Have histologically-confirmed metastatic breast cancer not deemed amenable to curative surgery or curative radiation therapy
Life expectancy of ? 6 months
Subjects must have adequate organ and marrow function
Suitable candidate for AI, including the ability to swallow and absorb oral agents
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 3
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion criteria:
Any of the following would exclude the subject from participation in the study:

Concurrent enrollment in another clinical study testing an investigational agent or
intervention for cancer treatment or prevention
Subject directly involved with the conduct of the study or an immediate family
member of any such individual
Subjects who received prior chemotherapy, hormonal therapy, immunotherapy or
biologic therapy for advanced or metastatic disease (except Prior adjuvant therapy with an AI is allowed, provided treatment ended at least 1 year prior to the first dose of therapy; Prior treatment with tamoxifen is allowed, provided treatment ended at least; 1 week prior to the first dose of therapy; Prior neoadjuvant and/or adjuvant chemotherapy for breast cancer is allowed)
History of allergy or reaction attributed to compounds of chemical or biologic
composition similar to those of MEDI-573 or AI
Subject for whom endocrine therapy of breast cancer is not appropriate (ie,
life-threatening or rapidly progressing metastatic disease)
Subjects with 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)
Known central nervous system metastases or leptomeningeal carcinomatosis
Evidence of spinal cord compression
Unresolved toxicities from prior therapy with the exception of alopecia that have not
resolved to ? Grade 1 (by National Cancer Institute Common Terminology Criteria
for Adverse Events [NCI CTCAE] version 4.0) at the time of starting study treatment
Receipt of any investigational therapy within 30 days or 5 half-lives, whichever is
longer, prior to receiving the first dose of study treatment
Previous treatment with agents that target the IGF receptor
Use of immunosuppressive medication other than steroids within 7 days before the
first dose of MEDI-573
History of another primary malignancy within 5 years prior to starting study treatment
except for curatively resected nonmelanoma skin cancer or carcinoma in situ of the
cervix
Poorly controlled diabetes mellitus as defined by investigator assessment and/or
hemoglobin A1c (HbA1c) > 8% within 21 days prior to randomization
History of cardiac disease including, but not limited to, congestive heart failure
> Class II New York Heart Association (see Appendix 3), active coronary artery
disease (eg, unstable angina pectoris), new onset angina pectoris, myocardial
infarction within the past 6 months, ventricular arrhythmias requiring antiarrhythmic
therapy, or uncontrolled hypertension within the last 6 months
Current active hepatic or biliary disease (with exception of subjects with Gilbert?s
syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease
per investigator assessment

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

Health Condition(s) or Problem(s) studied

Advanced Metastatic Breast Cancer (MBC)
MedDRA version: 14.0 Level: PT Classification code 10057654 Term: Breast cancer female System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.0 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: 14.0 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: equal
Concentration number: 25-

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

Main Objective: The primary objective of the dose-evaluation phase of this study (Phase 1b) is to evaluate the safety and tolerability of two doses of MEDI-573 in combination with an AI in patients with HR+, HER2-negative MBC

The primary objective of the randomization phase (Phase 2) of this study is to evaluate the PFS of subjects treated with MEDI-573 and AI versus treatment with AI alone.

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

Primary end point(s): The primary endpoint for the dose-evaluation phase is to assess the safety of MEDI-573 when used in combination with AI. Outcome measures include identification of a DLT and descriptions of AEs.

The primary endpoint for the randomization phase is PFS, which provides a direct measure of the effect of MEDI-573 on antitumor activity when used in combination with AI.

Secondary Outcome(s)

Secondary end point(s): Secondary end point for Safety and Tolerability of MEDI-573 in Phase 2: The safety endpoints include AEs, SAEs, and changes in clinical laboratory evaluations from baseline.

Pharmacokinetic Endpoint: Individual MEDI-573 concentrations will be tabulated by dose cohort along with descriptive statistics.

Pharmacodynamic Endpoints: Circulating IGF-I and IGF-II levels will be summarized by dose cohort and descriptive statistics will be used. The time course of circulating IGF will be graphed based on dose group. Exposure-response analysis will be conducted to explore the relationship between MEDI-573 exposure and circulating biomarkers (such as IGF-I and IGF-II).

Immunogenicity of MEDI-573: Analysis of IM results will be assessed by summarizing the number and percentage of subjects who develop detectable anti-MEDI-573 antibodies for all subjects entered in Phase 1b and Phase 2 (Arm 1 and Arm 2). The ADA titer will be reported for samples confirmed positive for the presence of anti-MEDI-573 antibodies. The effect of ADA on PK, pharmacodynamics, and safety will be evaluated

Secondary Efficacy Endpoints: The secondary endpoints for assessing antitumor activity include ORR, time to response, duration of response (DR), time to progression (TTP), and OS and change in tumor size. Response Evaluation Criteria in Solid Tumors v1.1 guidelines will be used to evaluate tumor response.

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 ID(s)

CD-ON-MEDI-573-1030

Source(s) of Monetary Support

MedImmune, LLC

Ethics review

Status: Approved
Approval date:
Contact: