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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00728949
Recruitment Status : Completed
First Posted : August 6, 2008
Last Update Posted : March 20, 2015
Information provided by (Responsible Party):
Eli Lilly and Company

July 31, 2008
August 6, 2008
March 20, 2015
August 2008
March 2012   (Final data collection date for primary outcome measure)
Progression-free survival (PFS) [ Time Frame: Approximately 24 months ]
Determine the PFS associated w/IMCA12 monotherapy and IMCA12 in combine w/an antiestrogen therapy in patients w/hormone receptor positive adv or metastatic breast cancer who experienced disease progress on antiestrogen. [ Time Frame: patients will be re evaluated every 8 weeks, with confirmatory assessment at least 4 weeks subsequent ]
Complete list of historical versions of study NCT00728949 on Archive Site
  • Objective response rate (ORR) [ Time Frame: 12 months ]
  • 12-month survival rate [ Time Frame: 12 months ]
  • Overall survival rate (OS) [ Time Frame: Approximately 24 months ]
  • Disease control rate (DCR) [ Time Frame: Approximately 24 months ]
  • Number of Participants with Adverse Events (AEs) [ Time Frame: Approximately 24 months ]
  • Changes in circulating tumor cell counts [ Time Frame: Approximately 24 months ]
To determine the objective response rate in the subset of pts with measurable disease. To determine 12 month survival rate, evaluate overall survival, determine the disease control rate, evaluate the safety, tolerability and adverse event [ Time Frame: 12 months ]
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A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer
Phase 2 Randomized, Multicenter Study of IMC-A12 as a Single Agent or in Combination With Antiestrogens in Postmenopausal Women With Hormone Receptor-Positive Advanced or Metastatic Breast Cancer After Progression on Antiestrogen Therapy
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.

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.

Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Metastatic Breast Cancer
  • Biological: IMC-A12 (cixutumumab)
    10 mg/kg I.V.
    Other Names:
    • Cixutumumab
    • LY3012217
  • Drug: tamoxifen
    Daily 20 mg, oral
  • Biological: Anastrozole
    Daily 1 mg, oral
  • Biological: Letrozole
    Daily 2.5 mg, oral
  • Drug: Exemestane
    Daily 25 mg, oral
  • Drug: Fulvestrant
    Monthly 250 mg, intramuscularly
  • Active Comparator: 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.
    • Biological: IMC-A12 (cixutumumab)
    • Drug: tamoxifen
    • Biological: Anastrozole
    • Biological: Letrozole
    • Drug: Exemestane
    • Drug: Fulvestrant
  • Experimental: IMC-A12 (cixutumumab)
    Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
    Intervention: Biological: IMC-A12 (cixutumumab)
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
February 2015
March 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
CP13-0604 ( Other Identifier: ImClone, LLC )
I5A-IE-JAEK ( Other Identifier: Eli Lilly and Company )
Not Provided
Not Provided
Eli Lilly and Company
Eli Lilly and Company
Not Provided
Study Director: 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) Eli Lilly and Company
Eli Lilly and Company
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP