Clinical trial NCT00728949: A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Keywords: breast cancer
Postmenopausal
Hormones
Antiestrogen
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2008-08-06
Enrollment: 93
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From randomization up to 35.1 Months
measure: Overall Survival (OS)
timeFrame: From randomization up to 36.5 Months
Secondary outcomes:
measure: Percentage of Participants With Complete Response (CR) and Partial Response (PR) (Objective Response Rate [ORR])
timeFrame: Randomization to PD up to 35.1 Months
measure: 12-Month Survival Rate
timeFrame: From randomization to until the date of first documented date of death from any cause within 12 months, assessed up to 35.1 months
measure: Percentage of Participants With Complete Response (CR) and Partial Response (PR) or Stable Disease (SD) Disease Control Rate [DCR])
timeFrame: Randomization to PD up to 35.1 Months
measure: Number of Participants Experiencing Adverse Events (AEs) in National Cancer Institute Common Toxicity Criteria for AE's (NCI-CTCAE) Version 3.0 Criteria for Adverse Events (NCI-CTCAE)
timeFrame: Randomization to End of Study up to 36.5 Months
measure: Changes in Circulating Tumor Cell Counts (CTS)
timeFrame: Approximately 24 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: ImClone Investigational Site
state: Arizona
city: Chicago
country: United States
facility: ImClone Investigational Site
state: Illinois
city: Westwood
country: United States
facility: ImClone Investigational Site
state: Kansas
city: Rochester
country: United States
facility: ImClone Investigational Site
state: Minnesota
city: Lebanon
country: United States
facility: ImClone Investigational Site
state: New Hampshire
city: Bronx
country: United States
facility: ImClone Investigational Site
state: New York
city: New York
country: United States
facility: ImClone Investigational Site
state: New York
city: Columbus
country: United States
facility: ImClone Investigational Site
state: Ohio
city: Nashville
country: United States
facility: ImClone Investigational Site
state: Tennessee
Study officials:
affiliation: Eli Lilly and Company
name: 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
References: