Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00728949
First received: July 31, 2008
Last updated: November 3, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Metastatic Breast Cancer
Biological: IMC-A12 (cixutumumab)
Drug: tamoxifen
Biological: Anastrozole
Biological: Letrozole
Drug: Exemestane
Drug: Fulvestrant
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Approximately 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • 12-month survival rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Overall survival rate (OS) [ Time Frame: Approximately 24 months ] [ Designated as safety issue: No ]
  • Disease control rate (DCR) [ Time Frame: Approximately 24 months ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events (AEs) [ Time Frame: Approximately 24 months ] [ Designated as safety issue: Yes ]
  • Changes in circulating tumor cell counts [ Time Frame: Approximately 24 months ] [ Designated as safety issue: No ]

Enrollment: 93
Study Start Date: August 2008
Estimated Study Completion Date: March 2015
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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
Experimental: IMC-A12 (cixutumumab)
Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).
Biological: IMC-A12 (cixutumumab)
10 mg/kg I.V.
Other Names:
  • Cixutumumab
  • LY3012217

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00728949

Locations
United States, Arizona
ImClone Investigational Site
Scottsdale, Arizona, United States, 85259
United States, Illinois
ImClone Investigational Site
Chicago, Illinois, United States, 60611
United States, Kansas
ImClone Investigational Site
Westwood, Kansas, United States, 66205
United States, Minnesota
ImClone Investigational Site
Rochester, Minnesota, United States, 55905-0002
United States, New Hampshire
ImClone Investigational Site
Lebanon, New Hampshire, United States, 03756
United States, New York
ImClone Investigational Site
Bronx, New York, United States, 10461
ImClone Investigational Site
New York, New York, United States, 10021
United States, Ohio
ImClone Investigational Site
Columbus, Ohio, United States, 43210
United States, Tennessee
ImClone Investigational Site
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00728949     History of Changes
Other Study ID Numbers: 13935, CP13-0604, I5A-IE-JAEK
Study First Received: July 31, 2008
Last Updated: November 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
breast cancer
Postmenopausal
Hormones
Antiestrogen

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014