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

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ClinicalTrials.gov Identifier: NCT00728949
Recruitment Status : Completed
First Posted : August 6, 2008
Results First Posted : June 5, 2018
Last Update Posted : June 5, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

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

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 93 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : August 2008
Actual Primary Completion Date : March 2012
Actual Study Completion Date : February 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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

Drug: Anastrozole
Daily 1 mg, oral

Drug: 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




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: From randomization up to 35.1 Months ]
    PFS is defined as the time from the date of randomization until date of objectively determined progressive disease (PD) or death due to any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a ≥20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions unequivocal progression of non-target lesions. Participants without documentation of progression or death will be censored at the date of last tumor assessment. The PFS will be estimated following the Kaplan-Meier method.

  2. Overall Survival (OS) [ Time Frame: From randomization up to 36.5 Months ]
    OS is defined as the interval between date of randomization and the date of death due to any cause. Participants who are alive at the time of study completion will be censored at the time the participants was last known to be alive.


Secondary Outcome Measures :
  1. Percentage of Participants With Complete Response (CR) and Partial Response (PR) (Objective Response Rate [ORR]) [ Time Frame: Randomization to PD up to 35.1 Months ]
    Best overall response of CR or PR was defined using RECIST v 1.0 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in sum of longest diameter (SOD) of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)*100.

  2. 12-Month Survival Rate [ Time Frame: From randomization to until the date of first documented date of death from any cause within 12 months, assessed up to 35.1 months ]
    The 12-month survival rate is defined as the percentage of participants who have not died 12 months after the date of randomization.

  3. Percentage of Participants With Complete Response (CR) and Partial Response (PR) or Stable Disease (SD) Disease Control Rate [DCR]) [ Time Frame: Randomization to PD up to 35.1 Months ]
    DCR is defined as percentage of participants with CR, PR, or SD using RECIST v 1.0 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in SOD of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)*100.

  4. 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) [ Time Frame: Randomization to End of Study up to 36.5 Months ]
    The NCI-CTCAE provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Severity will be graded as mild (grade 1), moderate (grade 2), severe (grade 3), or very severe (life threatening - grade 4). Clinically significant events were defined as serious and other non-serious adverse events related to study drug regardless of causality. A summary of serious and other non-serious adverse events is located in the Reported Adverse Event module.

  5. Changes in Circulating Tumor Cell Counts (CTS) [ Time Frame: Approximately 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00728949     History of Changes
Other Study ID Numbers: 13935
CP13-0604 ( Other Identifier: ImClone, LLC )
I5A-IE-JAEK ( Other Identifier: Eli Lilly and Company )
First Posted: August 6, 2008    Key Record Dates
Results First Posted: June 5, 2018
Last Update Posted: June 5, 2018
Last Verified: May 2018

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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Fulvestrant
Exemestane
Anastrozole
Tamoxifen
Estrogen Antagonists
Estrogen Receptor Modulators
Estrogen Receptor Antagonists
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents