Intermittent Letrozole Therapy in Postmenopausal Women With Metastatic Breast Cancer
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Intermittent letrozole therapy Letrozole 2.5 mg administered by mouth daily during each 28 day treatment cycle. Treatment is intermittent with possible breaks between each 28 day treatment cycle based on CA 15-3 or CA 27.29 levels. 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. |
Drug: Letrozole
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.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 2 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02215 |
Sponsors and Collaborators
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
- Novartis
Investigators
- Principal Investigator: Paul Goss, MD, PhD, Massachusetts General Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 07-109
Study Results
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. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Intermittent Letrozole Therapy |
|---|---|
| Arm/Group Description | 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. |
| Period Title: Overall Study | |
| STARTED | 3 |
| COMPLETED | 3 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Intermittent Letrozole Therapy |
|---|---|
| Arm/Group Description | 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. |
| Overall Participants | 3 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
1
33.3%
|
| >=65 years |
2
66.7%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
3
100%
|
| Male |
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
0
0%
|
| Not Hispanic or Latino |
3
100%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
3
100%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
3
100%
|
Outcome Measures
| Title | Number of Patients With Decline in Serum CA 15-3 (Carcinoma Antigen 15-3) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intermittent Letrozole Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 3 |
| Count of Participants [Participants] |
3
100%
|
| Title | Median Time to Disease Progression With Intermittent Letrozole. |
|---|---|
| Description | The median time to disease progression as determined by RECIST (Response Evaluation Criteria In Solid Tumors). |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Intermittent Letrozole Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 3 |
| Median (Full Range) [Months] |
47
|
| Title | Serum HER-2/Neu Levels and Serum/Plasma Angiogenic Mediators |
|---|---|
| Description | Measurements for the serum HER-2/neu (human epidermal growth factor receptor 2) levels and serum/plasma angiogenic mediators |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Study terminated prematurely due to slow accrual. Outcome measure data not available for analysis. |
| Arm/Group Title | Intermittent Letrozole Therapy |
|---|---|
| Arm/Group Description | 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. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | Duration of treatment and twelve weeks after stopping treatment. | |
|---|---|---|
| Adverse Event Reporting Description | Adverse events are recorded when reported by subjects and systematically evaluated through laboratory tests, physicals, and physician interviews every four weeks for the duration of treatment. Patients are followed for 12 weeks after removal from study or until death, whichever occurs first. | |
| Arm/Group Title | Intermittent Letrozole Therapy | |
| Arm/Group Description | Letrozole 2.5mg: Intermittently | |
All Cause Mortality |
||
| Intermittent Letrozole Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/3 (66.7%) | |
Serious Adverse Events |
||
| Intermittent Letrozole Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Intermittent Letrozole Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | |
| Blood and lymphatic system disorders | ||
| Hemoglobin | 2/3 (66.7%) | 24 |
| Lymphopenia | 1/3 (33.3%) | 12 |
| Hemorrhage-other | 1/3 (33.3%) | 13 |
| Endocrine disorders | ||
| Hot flashes | 3/3 (100%) | 54 |
| Gastrointestinal disorders | ||
| Constipation | 3/3 (100%) | 54 |
| Gastritis | 1/3 (33.3%) | 2 |
| Nausea | 3/3 (100%) | 54 |
| General disorders | ||
| Fatigue | 3/3 (100%) | 54 |
| Weight loss | 1/3 (33.3%) | 1 |
| Head/headache | 1/3 (33.3%) | 1 |
| Pain-other | 2/3 (66.7%) | 3 |
| Infections and infestations | ||
| Infection Gr0-2 neut, sinus | 1/3 (33.3%) | 1 |
| Metabolism and nutrition disorders | ||
| Alkaline phosphatase | 1/3 (33.3%) | 5 |
| ALT, SGPT | 1/3 (33.3%) | 6 |
| AST, SGOT | 1/3 (33.3%) | 6 |
| Creatinine | 1/3 (33.3%) | 5 |
| Hyperglycemia | 2/3 (66.7%) | 14 |
| Hyponatremia | 1/3 (33.3%) | 3 |
| Metabolic/Laboratory-other | 2/3 (66.7%) | 11 |
| Musculoskeletal and connective tissue disorders | ||
| Back, pain | 3/3 (100%) | 53 |
| Bone, pain | 3/3 (100%) | 54 |
| Chest wall, pain | 2/3 (66.7%) | 2 |
| Extremity-limb, pain | 1/3 (33.3%) | 3 |
| Joint, pain | 3/3 (100%) | 54 |
| Renal and urinary disorders | ||
| Renal/GU-other | 1/3 (33.3%) | 14 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 3/3 (100%) | 54 |
| Dyspnea | 3/3 (100%) | 54 |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 1/3 (33.3%) | 1 |
| Rash: acne/acneiform | 1/3 (33.3%) | 1 |
| Skin-other | 1/3 (33.3%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Paul Goss |
|---|---|
| Organization | Massachusetts General Hospital |
| Phone | 617-724-3118 |
| pgoss@mgh.harvard.edu |
- 07-109