A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer

NCT ID: NCT00728949

Last Updated: 2018-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 93 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-08-31
• Study Completion Date: 2015-02-28

Brief Summary

The purpose of this study is to determine whether IMC-A12 offers increased progression-free survival (PFS) associated with IMC-A12 monotherapy and IMC-A12 in combination with an antiestrogen therapy in patients with hormone receptor positive advanced or metastatic breast cancer that have experienced disease progression on antiestrogen therapy.

Detailed Description

Breast cancer is the most common form of malignancy affecting women worldwide, with approximately 178,480 new cases of invasive breast cancer and 62,030 new cases of in situ breast cancer expected in the United States (US) in 2007. Approximately 40,460 women are expected to die of breast cancer in the coming year, making the disease the second leading cause of cancer-related mortality among women (trailing only cancers of the lung and bronchus). However, thanks in part to recent advances in treatment, mortality rates associated with breast cancer have declined consistently since 1990.

Surgical resection and other treatments may particularly benefit patients whose disease is identified prior to metastasis; the 5-year survival rate for patients diagnosed with locoregionally advanced disease is 83%. However, women with distant metastases at diagnosis have a much poorer outlook, with a 5-year survival rate of only 26% and a median survival of approximately 2 years. Treatment of advanced disease may include first-line chemotherapy utilizing an anthracycline (eg, doxorubicin or epirubicin), antibody therapy, limited surgery, taxanes, and other cytotoxic agents. As complete responses are rare, these treatments are not generally employed as curative but in an effort to prolong life and provide symptom palliation.

Approximately two-thirds of all breast cancers are positive for expression of the estrogen receptor.For patients whose tumors are positive for this receptor or the progesterone receptor, the preferred first-line treatment comprises blockade of estradiol synthesis or hormone receptor activity using aromatase inhibitors or antiestrogen agents. Although endocrine therapies are useful and well-tolerated, most patients respond to this form of treatment for about 12-18 months before developing refractory disease. New therapies able to provide additional benefit to patients with hormone receptor-positive, antiestrogen-refractory, advanced and metastatic breast cancer are required.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMC-A12 (cixutumumab) + antiestrogen therapy

Participants will receive intravenous IMC-A12 10 mg/kg over 1 hour every 2 weeks, as well as the same dose and schedule of the last antiestrogen therapy to which their disease became refractory.

Group Type: ACTIVE_COMPARATOR

IMC-A12 (cixutumumab)

Intervention Type: BIOLOGICAL

10 mg/kg I.V.

tamoxifen

Intervention Type: DRUG

Daily 20 mg, oral

Anastrozole

Intervention Type: DRUG

Daily 1 mg, oral

Letrozole

Intervention Type: DRUG

Daily 2.5 mg, oral

Exemestane

Intervention Type: DRUG

Daily 25 mg, oral

Fulvestrant

Intervention Type: DRUG

Monthly 250 mg, intramuscularly

IMC-A12 (cixutumumab)

Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).

Group Type: EXPERIMENTAL

IMC-A12 (cixutumumab)

Intervention Type: BIOLOGICAL

10 mg/kg I.V.

Interventions

IMC-A12 (cixutumumab)

10 mg/kg I.V.

Intervention Type: BIOLOGICAL

tamoxifen

Daily 20 mg, oral

Intervention Type: DRUG

Anastrozole

Daily 1 mg, oral

Intervention Type: DRUG

Letrozole

Daily 2.5 mg, oral

Intervention Type: DRUG

Exemestane

Daily 25 mg, oral

Intervention Type: DRUG

Fulvestrant

Monthly 250 mg, intramuscularly

Intervention Type: DRUG

Other Intervention Names

Cixutumumab; LY3012217

Eligibility Criteria

Inclusion Criteria

• The patient has histologically or cytologically-confirmed invasive breast cancer, which at the time of study entry is either stage III (locally advanced) disease not amenable to curative therapy or stage IV disease. Histological confirmation of recurrent/metastatic disease is not required if clinical evidence of stage IV disease recurrence is available
• Tumors are positive for estrogen receptors (ER), progesterone receptors (PgR), or both (ie, 10% or more of infiltrating cancer cells exhibit nuclear staining for ER and/or PgR; positive biochemical test results are also acceptable)
• The patient has received prior antiestrogen therapy:

1. With at least one antiestrogen agent (with or without ovarian suppression) administered for ≥ 3 months in the adjuvant or metastatic setting; and

2. Experienced disease progression while on or within 12 months after receiving the last dose of endocrine therapy

• The patient is postmenopausal and/or meets at least one of the following criteria:

1. Age ≥ 18 years with an intact uterus and amenorrhea for ≥ 12 months, with estradiol and/or follicle-stimulating hormone (FSH) values in the postmenopausal range

2. History of bilateral oophorectomy

3. History of bilateral salpingo-oophorectomy

4. History of radiation castration and amenorrheic for ≥ 3 months

• The patient has fasting serum glucose < 120 mg/dL or below the ULN

Exclusion Criteria

• The patient has received more than two regimens of prior chemotherapy in the metastatic (or locally advanced and inoperable breast cancer) and adjuvant setting
• The patient has poorly controlled diabetes mellitus. Patients with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range (fasting glucose at study entry < 120 mg/dL or below ULN) and that they are on a stable dietary and/or therapeutic regimen for this condition
• The patient is known to be positive for infection with the human immunodeficiency virus

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

ImClone Investigational Site

Scottsdale, Arizona, United States

ImClone Investigational Site

Chicago, Illinois, United States

ImClone Investigational Site

Westwood, Kansas, United States

ImClone Investigational Site

Rochester, Minnesota, United States

ImClone Investigational Site

Lebanon, New Hampshire, United States

ImClone Investigational Site

New York, New York, United States

ImClone Investigational Site

The Bronx, New York, United States

ImClone Investigational Site

Columbus, Ohio, United States

ImClone Investigational Site

Nashville, Tennessee, United States

Countries

United States

Other Identifiers

CP13-0604

Identifier Type: OTHER

Identifier Source: secondary_id

I5A-IE-JAEK

Identifier Type: OTHER

Identifier Source: secondary_id

13935

Identifier Type: -

Identifier Source: org_study_id