Metastatic Breast CancerPhase 2NCT00728949
A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer
A Phase 2 study testing IMC-A12 (cixutumumab), tamoxifen and Anastrozole in people with Metastatic Breast Cancer, run by Eli Lilly and Company at 9 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- IMC-A12 (cixutumumab), tamoxifen and Anastrozole
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 93 participants
- Where
- 9 sitesUnited States
- Study dates
- Aug 2008to Feb 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
Show all 11Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
ImClone Investigational Site
Chicago, Illinois, 60611
ImClone Investigational Site
Columbus, Ohio, 43210
ImClone Investigational Site
Lebanon, New Hampshire, 03756
ImClone Investigational Site
Nashville, Tennessee, 37203
ImClone Investigational Site
New York, New York, 10021
ImClone Investigational Site
Rochester, Minnesota, 55905-0002
ImClone Investigational Site
Scottsdale, Arizona, 85259
ImClone Investigational Site
The Bronx, New York, 10461
ImClone Investigational Site
Westwood, Kansas, 66205
About this study
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
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.
Read the 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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- IMC-A12 (cixutumumab), tamoxifen, Anastrozole, Letrozole, Exemestane
- Keywords
- breast cancer, Postmenopausal, Hormones, Antiestrogen
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMC-A12 (cixutumumab)Biological
Also called Cixutumumab, LY3012217
10 mg/kg I.V.
tamoxifenDrug
Daily 20 mg, oral
AnastrozoleDrug
Daily 1 mg, oral
LetrozoleDrug
Daily 2.5 mg, oral
ExemestaneDrug
Daily 25 mg, oral
FulvestrantDrug
Monthly 250 mg, intramuscularly
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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). Receives: Biological: IMC-A12 (cixutumumab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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])
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.
Measured: Randomization to PD up to 35.1 Months
12-Month Survival Rate
The 12-month survival rate is defined as the percentage of participants who have not died 12 months after the date of randomization.
Measured: 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])
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.
Measured: 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)
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.
Measured: Randomization to End of Study up to 36.5 Months
Changes in Circulating Tumor Cell Counts (CTS)
Measured: Approximately 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2008 (estimated)
- Study startAug 2008
- Primary completionMar 2012
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 93 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- 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), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00728949
- Sponsor's protocol ID
- 13935
- Other IDs
- CP13-0604, I5A-IE-JAEK
- Status last verified
- May 2018
- First submitted
- 31 Jul 2008
- Last updated
- 6 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00728949
- Acronym / sponsor ID
- 13935
- Conditions
- Metastatic Breast Cancer
- Keywords
- breast cancer, Postmenopausal, Hormones, Antiestrogen
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- Aug 2008
- Primary completion
- Mar 2012 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 6 Aug 2008 (estimated)
- Results
- Posted 6 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IMC-A12 (cixutumumab) + antiestrogen therapy | Active comparator | Biological: IMC-A12 (cixutumumab), Drug: tamoxifen, Drug: Anastrozole, Drug: Letrozole, Drug: Exemestane, Drug: FulvestrantParticipants 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. |
| IMC-A12 (cixutumumab) | Experimental | Biological: IMC-A12 (cixutumumab)Participants will receive only IMC-A12 (10 mg/kg over 1 hour every 2 weeks). |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- The patient is postmenopausal and/or meets at least one of the following criteria:
- The patient has fasting serum glucose < 120 mg/dL or below the ULN
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IMC-A12 (cixutumumab)Also: Cixutumumab, LY301221710 mg/kg I.V. | Biological | IMC-A12 (cixutumumab), IMC-A12 (cixutumumab) + antiestrogen therapy |
| tamoxifenDaily 20 mg, oral | Drug | IMC-A12 (cixutumumab) + antiestrogen therapy |
| AnastrozoleDaily 1 mg, oral | Drug | IMC-A12 (cixutumumab) + antiestrogen therapy |
| LetrozoleDaily 2.5 mg, oral | Drug | IMC-A12 (cixutumumab) + antiestrogen therapy |
| ExemestaneDaily 25 mg, oral | Drug | IMC-A12 (cixutumumab) + antiestrogen therapy |
| FulvestrantMonthly 250 mg, intramuscularly | Drug | IMC-A12 (cixutumumab) + antiestrogen therapy |
Primary outcome
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.
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.
5 secondary outcomes
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
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
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
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
Changes in Circulating Tumor Cell Counts (CTS)
Time frame: Approximately 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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) study director
Eli Lilly and Company
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IMC-A12 (cixutumumab), tamoxifen and Anastrozole in people with Metastatic Breast Cancer, run by Eli Lilly and Company at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: From randomization up to 35.1 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2018.