Breast Cancer
Conditions
Brief summary
To evaluate the antitumor activity, toxicity, and effectiveness of the combination of goserelin (Zoladex) and anastrozole (Arimidex) in the treatment of premenopausal women with hormone receptor positive metastatic carcinoma of the breast.
Detailed description
Pre-menopausal women with estrogen and/or progesterone receptor positive, metastatic or recurrent breast cancer were enrolled and treated with goserelin (Zoladex) monthly and began anastrozole (Arimidex) daily for 21 days following the first injection of goserelin. Participants continued on treatment until disease progression or unacceptable toxicity.
Interventions
Anastrozole is a prescription hormonal treatment that helps fight breast cancer by lowering the amount of estrogen in the body. It is a non-steroidal aromatase inhibitor, which significantly lowers serum estradiol (estrogen) concentrations, without interfering with the formation of adrenal corticosteroids or aldosterone
Goserelin is a palliative treatment of advanced breast cancer in pre- and perimenopausal women
Sponsors
AstraZeneca
Stanford University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Histologically-confirmed, bi-dimensionally measurable, recurrent or metastatic carcinoma of the breast that is progressive * Premenopausal, defined as any of: 1. Last menstrual period within 3 months, or 2. Post-hysterectomy without bilateral oophorectomy and with follicle-stimulating hormone (FSH) in the premenopausal range, or, 3. If tamoxifen administered within the past 3 months, plasma estradiol must be in the premenopausal range * Either positive estrogen and/or progesterone receptor determination by Immunohistochemistry (IHC) or competitive binding assay on metastatic disease, or if not performed on their metastatic disease a positive result on their primary breast cancer specimen. * Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * Granulocytes \> 1500/mm\^3 * Platelets \> 100,000/mm\^3 * Serum glutamic oxaloacetic transaminase (SGOT) \< 2.5 x upper limit of normal * Total bilirubin \< 1.5 mg/dL * May have received irradiation to bony sites of disease for pain control or for prevention of fracture. The irradiated site(s) will NOT be evaluable for disease response. * Must be using effective contraception or not be of childbearing potential * Signed written informed consent INCLUSION CRITERIA * Active, unresolved infection * Active malignancy other than breast cancer, in situ carcinoma of the cervix, or non-melanomatous skin cancers in the past 5 years * Prior treatment with an aromatase inhibitor or inactivator * Prior treatment with an luteinizing hormone-releasing hormone (LH/RH) agonist/antagonist * Adjuvant chemotherapy within 6 months of study entry. * Received chemotherapy or hormonal therapy in the 3 weeks prior to enrollment * Central nervous system metastasis * Lymphangitic pulmonary metastasis * Pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 3 months | ORR was determined as the sum of the Complete Response (CR) rate + Partial Response (PR) rates. * CR = Complete disappearance of all clinically- or pathologically-detectable malignant disease for at least 4 weeks. * PR = ≥ 50% decrease in tumor size for at least 4 weeks, without any new lesion or any ≥ 25% increase in size of any lesion. All measurements by ruler or calipers. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rates | 6 months | The numbers of participants with metastatic breast cancer experiencing Complete Response (CR); Partial Response (PR); or Stable Disease (SD) after treatment with goserelin followed by anastrozole are reported. * CR = Complete disappearance of all clinically- or pathologically-detectable malignant disease for at least 4 weeks. * PR = ≥ 50% decrease in tumor size for at least 4 weeks, without any new lesion or any ≥ 25% increase in size of any lesion. * SD = No significant change in measurable or evaluable disease for at least 4 weeks. All measurements by ruler or calipers. |
| Time-to-Progression (TTP) | up to 63 months | Time-to-progression (TTP) was assessed as the median observed in the participant group. Progression of disease was considered, per protocol, to be ≤ 25% increase in the area of any malignant lesion greater than 2 square cm, or ≤ 25% increase in the sum of the products of the longest perpendicular diameters of individual lesions in a given organ, when compared to baseline values or after therapeutic response. |
| Clinical Benefit Rate | 6 months | The overall clinical benefit rate of goserelin followed by anastrozole was evaluated, as determined as the sum of the Complete Response (CR) rate + Partial Response (PR) rate + Stable Disease (SD) rate. * CR = Complete disappearance of all clinically- or pathologically-detectable malignant disease for at least 4 weeks. * PR = ≥ 50% decrease in tumor size for at least 4 weeks, without any new lesion or any ≥ 25% increase in size of any lesion. * SD = No significant change in measurable or evaluable disease for at least 4 weeks. All measurements by ruler or calipers. |
| Estradiol Suppression | 6 months | Plasma estradiol determinations were performed at baseline, 1 month, 3 months, and 6 months using the Coat-A-Count Estradiol competitive binding assay system, which has a calibrated range for estradiol of 20 to 3,600 pg/mL with an analytical sensitivity of 10 pg/mL. |
| Serious Adverse Events | 6 months | The toxicity of the treatment regimen of goserelin followed by anastrozole is estimated by the rate of Serious Adverse Events (SAEs) that occurred during the course of the study. |
| Overall Survival (OS) | up to 63 months | Overall survival (OS) was assessed as the median observed in the participants receiving goserelin followed by anastrozole. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anastrozole + Goserelin Participants received goserelin 3.6 mg subcutaneously monthly. Beginning on Day 22 after the first dose of goserelin, participants began taking anastrozole 1 mg orally daily. No dose attenuation or escalation was allowed for either goserelin or anastrozole. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Not eligible (no treatment) | 1 |
| Overall Study | Subject withdrawal (no treatment) | 1 |
| Overall Study | Underwent oophorectomy (no treatment) | 1 |
Baseline characteristics
| Characteristic | Anastrozole + Goserelin |
|---|---|
| Age, Continuous | 43 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 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 | 1 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 15 / 32 |
| other Total, other adverse events | 32 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR was determined as the sum of the Complete Response (CR) rate + Partial Response (PR) rates. * CR = Complete disappearance of all clinically- or pathologically-detectable malignant disease for at least 4 weeks. * PR = ≥ 50% decrease in tumor size for at least 4 weeks, without any new lesion or any ≥ 25% increase in size of any lesion. All measurements by ruler or calipers.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anastrozole + Goserelin | Objective Response Rate (ORR) | 37.5 percentage of participants |
Secondary
Clinical Benefit Rate
The overall clinical benefit rate of goserelin followed by anastrozole was evaluated, as determined as the sum of the Complete Response (CR) rate + Partial Response (PR) rate + Stable Disease (SD) rate. * CR = Complete disappearance of all clinically- or pathologically-detectable malignant disease for at least 4 weeks. * PR = ≥ 50% decrease in tumor size for at least 4 weeks, without any new lesion or any ≥ 25% increase in size of any lesion. * SD = No significant change in measurable or evaluable disease for at least 4 weeks. All measurements by ruler or calipers.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anastrozole + Goserelin | Clinical Benefit Rate | 71.9 percentage of participants |
Secondary
Estradiol Suppression
Plasma estradiol determinations were performed at baseline, 1 month, 3 months, and 6 months using the Coat-A-Count Estradiol competitive binding assay system, which has a calibrated range for estradiol of 20 to 3,600 pg/mL with an analytical sensitivity of 10 pg/mL.
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Anastrozole + Goserelin | Estradiol Suppression | Mean at Baseline | 74.7 pg/mL estradiol |
| Anastrozole + Goserelin | Estradiol Suppression | Mean at 1 month treatment | 20.8 pg/mL estradiol |
| Anastrozole + Goserelin | Estradiol Suppression | Mean at 3 months treatment | 18.7 pg/mL estradiol |
| Anastrozole + Goserelin | Estradiol Suppression | Mean at 6 months treatment | 14.8 pg/mL estradiol |
Secondary
Overall Survival (OS)
Overall survival (OS) was assessed as the median observed in the participants receiving goserelin followed by anastrozole.
Time frame: up to 63 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anastrozole + Goserelin | Overall Survival (OS) | NA months |
Secondary
Response Rates
The numbers of participants with metastatic breast cancer experiencing Complete Response (CR); Partial Response (PR); or Stable Disease (SD) after treatment with goserelin followed by anastrozole are reported. * CR = Complete disappearance of all clinically- or pathologically-detectable malignant disease for at least 4 weeks. * PR = ≥ 50% decrease in tumor size for at least 4 weeks, without any new lesion or any ≥ 25% increase in size of any lesion. * SD = No significant change in measurable or evaluable disease for at least 4 weeks. All measurements by ruler or calipers.
Time frame: 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Anastrozole + Goserelin | Response Rates | Stable Disease (SD) | 11 Participants |
| Anastrozole + Goserelin | Response Rates | Complete Response (CR) | 1 Participants |
| Anastrozole + Goserelin | Response Rates | Partial Response (PR) | 11 Participants |
Secondary
Serious Adverse Events
The toxicity of the treatment regimen of goserelin followed by anastrozole is estimated by the rate of Serious Adverse Events (SAEs) that occurred during the course of the study.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Anastrozole + Goserelin | Serious Adverse Events | 0 Serious Adverse Events (SAEs) |
Secondary
Time-to-Progression (TTP)
Time-to-progression (TTP) was assessed as the median observed in the participant group. Progression of disease was considered, per protocol, to be ≤ 25% increase in the area of any malignant lesion greater than 2 square cm, or ≤ 25% increase in the sum of the products of the longest perpendicular diameters of individual lesions in a given organ, when compared to baseline values or after therapeutic response.
Time frame: up to 63 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Anastrozole + Goserelin | Time-to-Progression (TTP) | 8.3 months |