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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT01446159
First received: September 12, 2011
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer
Drug: MEDI-573
Drug: Aromatase Inhibitor
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Phase Ib: Safety and tolerability of 2 dose levels of MEDI-573 combined with AI [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]
    The primary objective of the dose-evaluation phase 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. Specific endpoints: number of subjects with AEs, SAEs, and DLTs.

  • Phase 2 (Randomization Phase): Progression-free survival [ Time Frame: 26 months ] [ Designated as safety issue: No ]
    The primary objective of the randomization phase 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.


Secondary Outcome Measures:
  • safety and tolerability of MEDI-573 in combination with an AI [ Time Frame: 26 months ] [ Designated as safety issue: Yes ]
    To describe the safety and tolerability of MEDI-573 when used in combination with an AI. Specific endpoints: Number of subjects with AEs and SAEs.

  • anti-tumor activity of MEDI-573 when used in combination with an AI [ Time Frame: 26 months ] [ Designated as safety issue: No ]
    To evaluate the anti-tumor activity of MEDI-573 when used in combination with an AI versus treatment with an AI alone. Specific endpoints: Objective response rate, time to response, duration of response, time to progression, and change in tumor size.

  • overall survival (OS) [ Time Frame: 36+ months ] [ Designated as safety issue: No ]
    To evaluate overall survival (OS) in subjects treated with MEDI-573 when used in combination with an AI versus treatment with an AI alone.

  • pharmacokinetics (PK) of MEDI-573 [ Time Frame: 26 months ] [ Designated as safety issue: No ]
    To describe the pharmacokinetics (PK) of MEDI-573 when used in combination with an AI. Specific endpoints: AUC, Cmax, systemic clearance, and half-life.

  • Pharmacodynamics of MEDI-573 [ Time Frame: 26 months ] [ Designated as safety issue: No ]
    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)

  • Immunogenicity of MEDI-573 [ Time Frame: 26 months ] [ Designated as safety issue: No ]
    To evaluate the immunogenicity (IM) of MEDI-573 when used in combination with an AI. Specific endpoints: Number of patients who develop detectable anti-MEDI-573 antibodies.


Estimated Enrollment: 234
Study Start Date: June 2011
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose evaluation Cohort A
MEDI-573 in combination with aromatase Inhibitor
Drug: MEDI-573
MEDI-573
Drug: Aromatase Inhibitor
aromatase inhibitor
Experimental: Dose evaluation Cohort B
MEDI-573 in combination with aromatase Inhibitor
Drug: MEDI-573
MEDI-573
Drug: Aromatase Inhibitor
aromatase inhibitor
Experimental: Dose Evaluation Cohort C
MEDI-573 in combination with aromatase Inhibitor
Drug: MEDI-573
MEDI-573
Drug: Aromatase Inhibitor
aromatase inhibitor
Experimental: Randomized Arm 1
MEDI-573 in combination with aromatase Inhibitor
Drug: MEDI-573
MEDI-573
Drug: Aromatase Inhibitor
aromatase inhibitor
Active Comparator: Randomized Arm 2
aromatase inhibitor alone
Drug: Aromatase Inhibitor
aromatase inhibitor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01446159

  Show 79 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Jennifer McDevitt, PharmD, Ph.D. MedImmune LLC
  More Information

No publications provided

Responsible Party: MedImmune LLC
ClinicalTrials.gov Identifier: NCT01446159     History of Changes
Other Study ID Numbers: CD-ON-MEDI-573-1030
Study First Received: September 12, 2011
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by MedImmune LLC:
MEDI-573, breast cancer, metastatic, aromatase inhibitor, anti-IGF

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 24, 2014