Breast Cancer
Conditions
Keywords
aromatase inhibitor, CA 15-3, Hormone receptor positive
Brief summary
The purpose of this research study is to study the effects of using aromatase inhibitor (AI) therapy intermittently on participants with breast cancer. AIs are a class of drugs used to treat breast cancer in postmenopausal women. They work by decreasing the level of estrogen, which is believed to stimulate the growth of tumor tissue. Breast cancer that progresses despite therapy with an AI is thought to have become resistant to AI therapy. There is scientific evidence to suggest that resistant breast cancer cells learn to grow at the very low levels of estrogen present on AI therapy, and that increasing estrogen levels even slightly by stopping AI therapy may inhibit the breast cancer cells.
Detailed description
* This study involves treating participants with intermittent AI therapy. The AI will be stopped at the time they enter the study. We plan on monitoring a marker in the participants blood called CA 15-3 (or CA 27.29) every 4 weeks to help us make a decision of when to re-start treatment with letrozole (femara). This marker is known to rise when disease is progressing and drop when the disease is responding to treatment. We will be stopping and re-starting therapy based on the changes of CA 15-3 in the participants blood. * In addition to bloodwork, the following tests and procedures will be performed on a monthly basis: medical history; physical examination and performance status. * Every 8 weeks the following will be performed: Tumor assessment by physical exam (if possible); Chest x-ray or CT scan or chest; CT scans of abdomen and pelvis; and bone scan.
Interventions
DRUGLetrozole
Treatment is intermittent with possible breaks between each 28 day treatment cycle if CA 15-3 or CA 27.29 level that has decreased by at least 50% of that individual patient's baseline or peak level on firstline letrozole or anastrozole therapy or has decreased into the normal reference range per institutional parameters. Letrozole or anastrozole therapy will be interrupted until CA 15-3 or CA 27.29 levels rise by at least 25% above trough CA 15-3 or CA 27.29 level. If the trough level is in the normal reference range then the CA 15-3 or CA 27.29 must rise into the normal reference range.
Sponsors
Dana-Farber Cancer Institute
Novartis
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female * 18 years of age or older * Postmenopausal * Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease this is not considered amenable to curative treatment with elevation of CA 15-3 documented at the time of diagnosis of metastatic disease and prior to initiation of letrozole or anastrozole therapy * Current letrozole or anastrozole monotherapy with a documented CA 15-3 level that has decreased by at least 50% of the patients baseline * Letrozole or anastrozole must be discontinued at the time of study enrollment * Evidence of hormone sensitivity of primary or secondary tissue. * Measurable or nonmeasurable (but evaluable-defined as nontarget lesions) disease according to modified RECIST * Prior antiestrogen therapies including tamoxifen, steroidal AIs, nonsteroidal AIs, or fulvestrant in the adjuvant setting is allowed provided the patient is currently on letrozole or anastrozole monotherapy as first-line therapy for metastatic disease * Life expectancy of greater than 3 months * ECOG (Eastern Cooperative Oncology Group) Performance Status of 0,1, or 2 * Normal organ and marrow function as outlined in protocol
Exclusion criteria
* Premenopausal * Trastuzumab or biologic therapy within 2 weeks * Prior or planned radiation therapy to a site of evaluable disease in the event that the site is the only site of evaluable disease * Concomitant anticancer treatments including trastuzumab, chemotherapy, or other biologic agents other than letrozole or anastrozole therapy * Chronic bisphosphonates for hypercalcemia or prevention of bone metastases. * Treatment with non-approved or investigational agent within 2 weeks before study entry * Presence of life-threatening metastatic disease, defined as extensive hepatic involvement, or past or present brain or leptomeningeal involvement, or symptomatic pulmonary lymphangitic spread * Patients who are highly symptomatic from their breast cancer, or who require urgent palliative chemotherapy, as decided by their treating physician * Previous or current systemic malignancy within the past five years, except for contralateral breast carcinoma, in situ carcinoma of the cervix treated by cone biopsy, or adequately treated basal or squamous cell carcinoma of the skin. * Any severe concomitant condition believed to render subject undesirable for participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Decline in Serum CA 15-3 (Carcinoma Antigen 15-3) | 3 years | The Number of patients that have have a response of a decrease in CA 15-3 or CA 27.29 levels by at least 50% of that individual patient's baseline or peak level after re-introducing Letrozole therapy following a break in therapy as described in the intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Disease Progression With Intermittent Letrozole. | 3 years | The median time to disease progression as determined by RECIST (Response Evaluation Criteria In Solid Tumors). |
| Serum HER-2/Neu Levels and Serum/Plasma Angiogenic Mediators | 2 years | Measurements for the serum HER-2/neu (human epidermal growth factor receptor 2) levels and serum/plasma angiogenic mediators |
Countries
United States
Participant flow
Recruitment details
Postmenopausal patients with ER-positive (ER+) metastatic breast cancer (MBC) that were enrolled on an institutional review board (IRB) approved, phase II, multicenter clinical trial protocol (NCT00549822) evaluating intermittent AI (Aromatase Inhibitor) therapy. The study opened to accrual August 29, 2006 and closed to accrual on May 17, 2010.
Participants by arm
| Arm | Count |
|---|---|
| Intermittent Letrozole Therapy Letrozole 2.5mg: Intermittently
Letrozole 2.5 mg administered by mouth each day during each 28 day treatment cycle. Treatment is intermittent with possible breaks between each 28 day treatment cycle. Letrozole is administered until the participant has disease progression as determined by RECIST (Response Evaluation Criteria In Solid Tumors), experiences severe side effects, or decides to stop treatment. | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Intermittent Letrozole Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Number of Patients With Decline in Serum CA 15-3 (Carcinoma Antigen 15-3)
The Number of patients that have have a response of a decrease in CA 15-3 or CA 27.29 levels by at least 50% of that individual patient's baseline or peak level after re-introducing Letrozole therapy following a break in therapy as described in the intervention.
Time frame: 3 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intermittent Letrozole Therapy | Number of Patients With Decline in Serum CA 15-3 (Carcinoma Antigen 15-3) | 3 Participants |
Secondary
Median Time to Disease Progression With Intermittent Letrozole.
The median time to disease progression as determined by RECIST (Response Evaluation Criteria In Solid Tumors).
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Intermittent Letrozole Therapy | Median Time to Disease Progression With Intermittent Letrozole. | 47 Months |
Secondary
Serum HER-2/Neu Levels and Serum/Plasma Angiogenic Mediators
Measurements for the serum HER-2/neu (human epidermal growth factor receptor 2) levels and serum/plasma angiogenic mediators
Time frame: 2 years
Population: Study terminated prematurely due to slow accrual. Outcome measure data not available for analysis.