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

MedImmune

Status and phase: Completed; Phase 2

Conditions: Hormone-sensitive, HER-2 Negative Metastatic Breast Cancer

Treatments: Drug: Aromatase Inhibitor; Drug: MEDI-573

Study type: Interventional

Funder types: Industry

Identifiers

NCT01446159

CD-ON-MEDI-573-1030

Details and patient eligibility

About

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.

Full 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).

Enrollment: 188 patients

Sex: Female

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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188 participants in 4 patient groups

MEDI-573 10 mg/kg + AI

Experimental group

Description:

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.

Treatment:

Drug: Aromatase Inhibitor

Drug: MEDI-573

MEDI-573 30 mg/kg + AI

Experimental group

Description:

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.

Treatment:

Drug: Aromatase Inhibitor

Drug: MEDI-573

MEDI-573 45 mg/kg + AI

Experimental group

Description:

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.

Treatment:

Drug: Aromatase Inhibitor

Drug: MEDI-573

Aromatase Inhibitor

Experimental group

Description:

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.

Treatment:

Drug: Aromatase Inhibitor