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

NCT00728949 | Completed Phase 2 Results

• 3 other identifiers: 13935CP13-0604I5A-IE-JAEK
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 9

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.

Conditions

Metastatic Breast Cancer

Keywords

breast cancer; Postmenopausal; Hormones; Antiestrogen

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival (PFS)

  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.

  From randomization up to 35.1 Months

• Overall Survival (OS)

  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.

  From randomization up to 36.5 Months

Secondary Outcomes (5)

• Percentage of Participants With Complete Response (CR) and Partial Response (PR) (Objective Response Rate [ORR])

  Randomization to PD up to 35.1 Months

• 12-Month Survival Rate

  From randomization to until the date of first documented date of death from any cause within 12 months, assessed up to 35.1 months

• Percentage of Participants With Complete Response (CR) and Partial Response (PR) or Stable Disease (SD) Disease Control Rate [DCR])

  Randomization to PD up to 35.1 Months

• 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)

  Randomization to End of Study up to 36.5 Months

• Changes in Circulating Tumor Cell Counts (CTS)

  Approximately 24 months

Study Arms (2)

IMC-A12 (cixutumumab) + antiestrogen therapy

ACTIVE COMPARATOR

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; Drug: Anastrozole; Drug: Letrozole; Drug: Exemestane; Drug: Fulvestrant

IMC-A12 (cixutumumab)

EXPERIMENTAL

Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks).

Biological: IMC-A12 (cixutumumab)

Interventions

IMC-A12 (cixutumumab) BIOLOGICAL

10 mg/kg I.V.

Also known as: Cixutumumab, LY3012217

IMC-A12 (cixutumumab); IMC-A12 (cixutumumab) + antiestrogen therapy

tamoxifen DRUG

Daily 20 mg, oral

IMC-A12 (cixutumumab) + antiestrogen therapy

Anastrozole DRUG

Daily 1 mg, oral

IMC-A12 (cixutumumab) + antiestrogen therapy

Letrozole DRUG

Daily 2.5 mg, oral

IMC-A12 (cixutumumab) + antiestrogen therapy

Exemestane DRUG

Daily 25 mg, oral

IMC-A12 (cixutumumab) + antiestrogen therapy

Fulvestrant DRUG

Monthly 250 mg, intramuscularly

IMC-A12 (cixutumumab) + antiestrogen therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• With at least one antiestrogen agent (with or without ovarian suppression) administered for ≥ 3 months in the adjuvant or metastatic setting; and
• 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:
• 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
• History of bilateral oophorectomy
• History of bilateral salpingo-oophorectomy
• History of radiation castration and amenorrheic for ≥ 3 months
• The patient has fasting serum glucose \< 120 mg/dL or below the ULN

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (9)

ImClone Investigational Site

Scottsdale, Arizona, 85259, United States

Location

ImClone Investigational Site

Chicago, Illinois, 60611, United States

Location

ImClone Investigational Site

Westwood, Kansas, 66205, United States

Location

ImClone Investigational Site

Rochester, Minnesota, 55905-0002, United States

Location

ImClone Investigational Site

Lebanon, New Hampshire, 03756, United States

Location

ImClone Investigational Site

New York, New York, 10021, United States

Location

ImClone Investigational Site

The Bronx, New York, 10461, United States

Location

ImClone Investigational Site

Columbus, Ohio, 43210, United States

Location

ImClone Investigational Site

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

cixutumumab; Tamoxifen; Anastrozole; Letrozole; exemestane; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

There is a difference of 6 participants for treatment groups of IMC-A12 (Cixutumumab) + Antiestrogen and IMC-A12 (Cixutumumab) of ITT population and Safety population due to planned treatment (based on randomization) differed from actual treatment.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2008
• First Posted: August 6, 2008
• Study Start: August 1, 2008
• Primary Completion: March 1, 2012
• Study Completion: February 1, 2015
• Last Updated: June 6, 2018
• Results First Posted: June 6, 2018

Record last verified: 2018-05

Locations

US (9)