Clinical trial NCT00728949
Conditions: Metastatic Breast Cancer
Keywords: breast cancer Postmenopausal Hormones Antiestrogen
Sponsor: Eli Lilly and Company
Start date: 2008-08-01; Completion date: 2015-02-01
Enrollment: 93 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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. arm 2: Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
Interventions: intervention 1: IMC-A12 (cixutumumab) intervention 2: tamoxifen intervention 3: Anastrozole intervention 4: Letrozole intervention 5: Exemestane intervention 6: Fulvestrant
Intervention descriptions: intervention 1: 10 mg/kg I.V. intervention 2: Daily 20 mg, oral intervention 3: Daily 1 mg, oral intervention 4: Daily 2.5 mg, oral intervention 5: Daily 25 mg, oral intervention 6: Monthly 250 mg, intramuscularly

Protocol documents: