Breast Cancer
Conditions
Keywords
Postmenopausal, Women
Brief summary
The purpose of this trial is to evaluate time to progression in women with hormone responsive advanced breast cancer treated with a combination of exemestane and fulvestrant.
Interventions
DRUGExemestane
25 mg orally per day
DRUGFulvestrant
250 mg IM starting on Day 8 and then every 28 days.
Sponsors
Pfizer
Ohio State University Comprehensive Cancer Center
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
* Proven breast cancer * Metastatic or locally advanced breast cancer * Hormonally responsive disease defined as estrogen (ER) and/ or progesterone receptor (PR) positive (\>10% staining by immunohistochemistry) * Postmenopausal status * No more than 1 prior chemotherapy for stage IV metastatic breast cancer allowed * ECOG (Eastern Cooperative Oncology Group) performance status 0-2 * Adequate organ function *
Exclusion criteria
* No prior Exemestane or Fulvestrant * Uncontrolled intercurrent illness including but not limited to: * ongoing or active infection * symptomatic congestive heart failure * unstable angina pectoris * cardiac arrhythmia * myocardial infarction within the last 3 months * psychiatric illness/social situations that would limit compliance with study * Lymphangitic pulmonary disease; carcinomatous meningitis, bone marrow only metastases; and a rising tumor marker without any other site of metastatic disease. * Presence of bleeding diathesis or coagulopathy, patients requiring coumadin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) in Women With Hormone Responsive Advanced Breast Cancer Treated With Combination of Exemestane and Fulvestrant. | Every 2 cycles up to 2 years | TTP is defined as the time from first treatment to objective evidence of progression on the basis of radiological evaluation and/or physical exam (if physical examination identifies a site of measurable disease). 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) | Every 2 cycles, up to 1 year | Response and progression was evaluated after every 2 cycles by physical examination and imaging studies using the international RECIST criteria. Complete Response (CR), Partial Response (PR), Overall Response Rate (ORR), Stable Disease (SD), Progressive Disease (PD). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); PD, 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; Complete Response (CR), Disappearance of all target lesions; Overall Response Rate (ORR), CR+PR |
| Maximum Plasma Concentration (Cmax) of Exemestane When Administered Alone and With Fulvestrant | Day 7 and Day 120 | 5 mL of venous whole blood was obtained before dosing and then at 1, 2, 4, 6, 8, and 24 hours after exemestane ingestion on each of the 2 time points. |
| Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels | Prestudy, Day 7 and Day 120 | — |
Countries
United States
Participant flow
Recruitment details
Patients were enrolled between November 2005 and December 2009
Participants by arm
| Arm | Count |
|---|---|
| Exemestane and Fulvestrant Combination of daily exemestane 25 mg with monthly 250 mg Fulvestrant injection
Exemestane: 25 mg orally per day
Fulvestrant: 250 mg IM starting on Day 8 and then every 28 days. | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | Exemestane and Fulvestrant |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 11 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 58 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 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 | 4 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 | 36 Participants |
| Region of Enrollment United States | 40 participants |
| Relapse and/or Progression >12 mo after completion adjuvant therapy | 9 participants |
| Relapse and/or Progression During adjuvant endocrine therapy | 14 participants |
| Relapse and/or Progression Never on adjuvant hormonal therapy | 9 participants |
| Relapse and/or Progression Presenting with de novo metastatic disease | 8 participants |
| Sex: Female, Male Female | 40 Participants |
| Sex: Female, Male Male | 0 Participants |
| Time From Primary Diagnosis to Metastatic Disease | 5 years |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 24 / 40 |
| serious Total, serious adverse events | 6 / 40 |
Outcome results
Primary
Time to Progression (TTP) in Women With Hormone Responsive Advanced Breast Cancer Treated With Combination of Exemestane and Fulvestrant.
TTP is defined as the time from first treatment to objective evidence of progression on the basis of radiological evaluation and/or physical exam (if physical examination identifies a site of measurable disease). 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
Time frame: Every 2 cycles up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Exemestane and Fulvestrant | Time to Progression (TTP) in Women With Hormone Responsive Advanced Breast Cancer Treated With Combination of Exemestane and Fulvestrant. | 6.9 months |
Secondary
Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels
Time frame: Prestudy, Day 7 and Day 120
Population: Increase in mean levels from baseline to day 120. Not all patients had the IGF-1 and IGFBP-3 levels present.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exemestane and Fulvestrant | Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels | Baseline | 119 ng/mL | Standard Deviation 41.1 |
| Exemestane and Fulvestrant | Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels | Day 7 | 141 ng/mL | Standard Deviation 55.1 |
| Exemestane and Fulvestrant | Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels | Day 120 | 161 ng/mL | Standard Deviation 61.2 |
| IGFBP-3 | Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels | Baseline | 4946 ng/mL | Standard Deviation 1188 |
| IGFBP-3 | Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels | Day 7 | 5273 ng/mL | Standard Deviation 1372 |
| IGFBP-3 | Examine the Effect of Exemestane + Fulvestrant on Serum IGF-1 and IGFPB-3 Levels | Day 120 | 5537 ng/mL | Standard Deviation 1166 |
Secondary
Maximum Plasma Concentration (Cmax) of Exemestane When Administered Alone and With Fulvestrant
5 mL of venous whole blood was obtained before dosing and then at 1, 2, 4, 6, 8, and 24 hours after exemestane ingestion on each of the 2 time points.
Time frame: Day 7 and Day 120
Population: Only 9 patients had evaluable PK data collected and analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Exemestane and Fulvestrant | Maximum Plasma Concentration (Cmax) of Exemestane When Administered Alone and With Fulvestrant | Exemestane Alone (Day 7) | 20.1 ng/ml | Standard Deviation 7.7 |
| Exemestane and Fulvestrant | Maximum Plasma Concentration (Cmax) of Exemestane When Administered Alone and With Fulvestrant | Exemestane + Fulvestrant (Day 120) | 21.2 ng/ml | Standard Deviation 11.1 |
p-value: 0.9102Wilcoxon (Mann-Whitney)
Secondary
Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease)
Response and progression was evaluated after every 2 cycles by physical examination and imaging studies using the international RECIST criteria. Complete Response (CR), Partial Response (PR), Overall Response Rate (ORR), Stable Disease (SD), Progressive Disease (PD). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); PD, 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; Complete Response (CR), Disappearance of all target lesions; Overall Response Rate (ORR), CR+PR
Time frame: Every 2 cycles, up to 1 year
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Exemestane and Fulvestrant | Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) | PR | 3 patients |
| Exemestane and Fulvestrant | Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) | ORR | 3 patients |
| Exemestane and Fulvestrant | Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) | SD ≥ 6 Mo | 17 patients |
| Exemestane and Fulvestrant | Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) | Overall Clinical Benefit | 20 patients |
| Exemestane and Fulvestrant | Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) | SD< 6 Mo | 8 patients |
| Exemestane and Fulvestrant | Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) | PD | 12 patients |
| Exemestane and Fulvestrant | Overall Clinical Benefit (Complete Response Rate, Partial Response and Stable Disease) | CR | 0 patients |