Trial Outcomes & Findings for Estradiol Suppression for the Treatment of Metastatic Breast Cancer in Premenopausal Women (NCT NCT00186121)

Last Updated: 2019-10-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

3 months

Results posted on

2019-10-07

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	35
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Subject withdrawal (no treatment)	1
Overall Study Underwent oophorectomy (no treatment)	1
Overall Study Not eligible (no treatment)	1

Baseline Characteristics

Estradiol Suppression for the Treatment of Metastatic Breast Cancer in Premenopausal Women

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Anastrozole + Goserelin n=32 Participants 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.
Age, Continuous	43 years n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 3 months

Outcome measures

Outcome measures
Measure	Anastrozole + Goserelin n=32 Participants 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.
Objective Response Rate (ORR)	37.5 percentage of participants Interval 21.0 to 56.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Anastrozole + Goserelin n=32 Participants 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.
Clinical Benefit Rate	71.9 percentage of participants Interval 53.0 to 86.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Anastrozole + Goserelin n=32 Participants 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.
Response Rates Complete Response (CR)	1 Participants
Response Rates Partial Response (PR)	11 Participants
Response Rates Stable Disease (SD)	11 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Anastrozole + Goserelin n=32 Participants 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.
Time-to-Progression (TTP)	8.3 months Interval 2.1 to The upper limit of the range for TTP was not determined / not reached.

SECONDARY outcome

Timeframe: up to 63 months

Overall survival (OS) was assessed as the median observed in the participants receiving goserelin followed by anastrozole.

Outcome measures

Outcome measures
Measure	Anastrozole + Goserelin n=32 Participants 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.
Overall Survival (OS)	NA months Interval 11.1 to The median and upper limit of the range for OS were not reached / not determined. The upper limit exceeded 63 months.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Anastrozole + Goserelin n=32 Participants 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.
Estradiol Suppression Mean at 1 month treatment	20.8 pg/mL estradiol Standard Deviation NA The study manuscript is the only source of these results data. The location of original study files is not known. The original data values are not available. Only the mean value without dispersion is known. No measure of dispersion is available.
Estradiol Suppression Mean at 3 months treatment	18.7 pg/mL estradiol Standard Deviation NA The study manuscript is the only source of these results data. The location of original study files is not known. The original data values are not available. Only the mean value without dispersion is known. No measure of dispersion is available.
Estradiol Suppression Mean at 6 months treatment	14.8 pg/mL estradiol Standard Deviation NA The study manuscript is the only source of these results data. The location of original study files is not known. The original data values are not available. Only the mean value without dispersion is known. No measure of dispersion is available.
Estradiol Suppression Mean at Baseline	74.7 pg/mL estradiol Standard Deviation NA The study manuscript is the only source of these results data. The location of original study files is not known. The original data values are not available. Only the mean value without dispersion is known. No measure of dispersion is available.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Anastrozole + Goserelin n=32 Participants 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.
Serious Adverse Events	0 Serious Adverse Events (SAEs)

Adverse Events

Anastrozole + Goserelin

Serious events: 0 serious events

Other events: 32 other events

Deaths: 15 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Anastrozole + Goserelin n=32 participants at risk 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.
Vascular disorders Hot flush	59.4% 19/32 • Number of events 19 • Up to 63 months
Musculoskeletal and connective tissue disorders Arthralgia	53.1% 17/32 • Number of events 17 • Up to 63 months
General disorders Fatigue	50.0% 16/32 • Number of events 16 • Up to 63 months
Nervous system disorders Headache	31.2% 10/32 • Number of events 10 • Up to 63 months
Skin and subcutaneous tissue disorders Alopecia	25.0% 8/32 • Number of events 8 • Up to 63 months
Nervous system disorders Neuropathy	18.8% 6/32 • Number of events 6 • Up to 63 months
Reproductive system and breast disorders Vaginal dryness	18.8% 6/32 • Number of events 6 • Up to 63 months
Gastrointestinal disorders Constipation	12.5% 4/32 • Number of events 4 • Up to 63 months
Respiratory, thoracic and mediastinal disorders Cough	12.5% 4/32 • Number of events 4 • Up to 63 months
Gastrointestinal disorders Diarrhea	12.5% 4/32 • Number of events 4 • Up to 63 months
Skin and subcutaneous tissue disorders Dry skin	12.5% 4/32 • Number of events 4 • Up to 63 months
Musculoskeletal and connective tissue disorders Myalgia	12.5% 4/32 • Number of events 4 • Up to 63 months
Gastrointestinal disorders Nausea	12.5% 4/32 • Number of events 4 • Up to 63 months
Psychiatric disorders Mood alteration	9.4% 3/32 • Number of events 3 • Up to 63 months
Skin and subcutaneous tissue disorders Rash	9.4% 3/32 • Number of events 3 • Up to 63 months
Respiratory, thoracic and mediastinal disorders Rhinitis	9.4% 3/32 • Number of events 3 • Up to 63 months
General disorders General disorders, other: Increased Sweating	9.4% 3/32 • Number of events 3 • Up to 63 months
Nervous system disorders Dizziness	6.2% 2/32 • Number of events 2 • Up to 63 months
Respiratory, thoracic and mediastinal disorders Dyspnea	6.2% 2/32 • Number of events 2 • Up to 63 months
General disorders Edema	6.2% 2/32 • Number of events 2 • Up to 63 months
Psychiatric disorders Insomnia	6.2% 2/32 • Number of events 2 • Up to 63 months
General disorders Pain	6.2% 2/32 • Number of events 2 • Up to 63 months
Reproductive system and breast disorders Vaginal discharge	6.2% 2/32 • Number of events 2 • Up to 63 months
Gastrointestinal disorders Vomiting	6.2% 2/32 • Number of events 2 • Up to 63 months
Investigations Weight loss	6.2% 2/32 • Number of events 2 • Up to 63 months
Injury, poisoning and procedural complications Bruising	3.1% 1/32 • Number of events 1 • Up to 63 months
General disorders Flu-like symptoms	3.1% 1/32 • Number of events 1 • Up to 63 months
Gastrointestinal disorders Gastrointestinal disorders - Other, cramping	3.1% 1/32 • Number of events 1 • Up to 63 months
Gastrointestinal disorders Gastrointestinal disorders - Other, Heart burn	3.1% 1/32 • Number of events 1 • Up to 63 months
Gastrointestinal disorders Rectal bleeding	3.1% 1/32 • Number of events 1 • Up to 63 months
Eye disorders Watering eyes	3.1% 1/32 • Number of events 1 • Up to 63 months
Eye disorders Blurred vision	3.1% 1/32 • Number of events 1 • Up to 63 months

Additional Information

Melinda Telli, MD

Stanford University Medical Center

Phone: 650-724-9533

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place