Trial Outcomes & Findings for RCT of Fixed vs Titrated Letrozole in Breast Cancer Patient Undergoing IVF (NCT NCT01035099)
NCT ID: NCT01035099
Last Updated: 2022-12-13
Results Overview
Mature oocyte yield in each group
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
41 participants
Primary outcome timeframe
1 to 2 months
Results posted on
2022-12-13
Participant Flow
41 subjects were enrolled; One subject 1 later withdrew consent prior to randomization.
Participant milestones
| Measure |
Titrated Dose Letrozole
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
Overall Study
STARTED
|
18
|
22
|
|
Overall Study
COMPLETED
|
18
|
22
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
RCT of Fixed vs Titrated Letrozole in Breast Cancer Patient Undergoing IVF
Baseline characteristics by cohort
| Measure |
Titrated Dose Letrozole
n=18 Participants
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=22 Participants
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
18 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
40 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
40 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=93 Participants
|
21 Participants
n=4 Participants
|
39 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
18 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
40 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 1 to 2 monthsPopulation: Only 39 subjects analyzed of 41 (1 subject later withdrew consent prior to randomization; 1 subject in the Fixed dose group had no oocytes harvested, so this measure could not be calculated for that patient).
Mature oocyte yield in each group
Outcome measures
| Measure |
Titrated Dose Letrozole
n=18 Participants
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=21 Participants
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
Mature Oocyte Yield
|
5.1 oocytes
Standard Deviation 8.4
|
7.9 oocytes
Standard Deviation 8.2
|
PRIMARY outcome
Timeframe: 1 to 2 monthsPopulation: Only 39 subjects analyzed of 41 (1 subject later withdrew consent prior to randomization; 1 subject in the Fixed dose group had no oocytes harvested, so this measure could not be calculated for that patient).
The percentage of mature oocyte obtained will be compared from both arms. Calculated as number of mature oocytes divided by number of oocytes retrieved (per patient).
Outcome measures
| Measure |
Titrated Dose Letrozole
n=18 Participants
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=21 Participants
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
Percent of Mature Oocyte Yield
|
0.29 percentage of mature oocytes
Standard Deviation 0.38
|
0.46 percentage of mature oocytes
Standard Deviation 0.41
|
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: This information was not recorded.
Cycle cancellation rate- participant
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 5 yearsPopulation: This information was not recorded.
5 year follow-up breast cancer recurrence rate
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: Only 40 subjects analyzed of 41 (1 subject later withdrew consent prior to randomization).
Peak Serum Estradiol Level (pg/ml)
Outcome measures
| Measure |
Titrated Dose Letrozole
n=18 Participants
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=22 Participants
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
Peak Serum Estradiol Level
|
603.1 pg/ml
Standard Deviation 213.4
|
771.1 pg/ml
Standard Deviation 401.1
|
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: Only 37 subjects analyzed of 41 (1 subject later withdrew consent prior to randomization; Three subjects in Titrated group did not have FSH recorded).
FSH ng/ml on Cycle Day 2
Outcome measures
| Measure |
Titrated Dose Letrozole
n=15 Participants
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=22 Participants
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
FSH ng/ml (Cycle Day 2)
|
5.9 ng/ml
Standard Deviation 2.0
|
5.8 ng/ml
Standard Deviation 1.6
|
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: Only 33 subjects analyzed of 41 (1 subject later withdrew consent prior to randomization; Three subjects in Titrated group did not have AMH recorded and 4 patients in the Fixed group did not have AMH recorded).
AMH ng/ml on Cycle Day 2
Outcome measures
| Measure |
Titrated Dose Letrozole
n=15 Participants
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=18 Participants
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
AMH ng/ml (Cycle Day 2)
|
2.1 ng/ml
Standard Deviation 1.6
|
2.4 ng/ml
Standard Deviation 1.4
|
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: This information was not recorded.
Antral follicle count
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: Only 40 subjects analyzed of 41 (1 subject later withdrew consent prior to randomization).
Total days of stimulation medications
Outcome measures
| Measure |
Titrated Dose Letrozole
n=18 Participants
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=22 Participants
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
Total Days Stimulation Medications
|
10.1 days
Standard Deviation 1.7
|
11.2 days
Standard Deviation 2.7
|
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: Only 40 subjects analyzed of 41 (1 subject later withdrew consent prior to randomization).
Total medication dose given
Outcome measures
| Measure |
Titrated Dose Letrozole
n=18 Participants
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=22 Participants
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
Total Medication Dose
|
34.0 mg
Standard Deviation 7.0
|
55.3 mg
Standard Deviation 14.3
|
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: Only 40 subjects analyzed of 41 (1 subject later withdrew consent prior to randomization).
Total number of oocytes retrieved
Outcome measures
| Measure |
Titrated Dose Letrozole
n=18 Participants
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=22 Participants
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
Total Number of Oocytes
|
17.1 oocytes
Standard Deviation 10.3
|
19.0 oocytes
Standard Deviation 11.2
|
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: This information was not recorded.
Number of follicles on day of Human Chorionic Gonadotrophin (HCG)
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: Only 39 subjects analyzed of 41 (1 subject later withdrew consent prior to randomization; One subject in Fixed group did not have this information recorded).
Number of fertilized oocytes among participants
Outcome measures
| Measure |
Titrated Dose Letrozole
n=18 Participants
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=21 Participants
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
Number of Fertilized Oocytes
|
3.7 fertlized oocytes
Standard Deviation 5.8
|
5.3 fertlized oocytes
Standard Deviation 6.4
|
SECONDARY outcome
Timeframe: 1 to 2 monthsPopulation: This information was not recorded.
Number of good quality embryos among participants
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 1 to 2 yearsPopulation: This information was not recorded.
Number of Subjects with Breast Cancer Recurrence at Year 1-2
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 2- 3 yearsPopulation: This information was not recorded.
Number of Subjects with Breast Cancer Recurrence at year 2-3
Outcome measures
Outcome data not reported
Adverse Events
Titrated Dose Letrozole
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Fixed Dose Letrozole
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Titrated Dose Letrozole
n=18 participants at risk
Patients who are randomized to the titrated dose of Letrozole, will start gonadotropins in the evening of day #2 of their menstrual cycle with injectable follicle stimulating hormone (FSH) and human menopausal gonadotropin (HMG). Oral Letrozole will be added to the stimulation in the following titrated regimen.
Letrozole: Letrozole titrated regimen may be started on day 2 of menstrual cycle:
Serum Estradiol level \<150 pg/ml- No Letrozole; Serum Estradiol Level 150-250 pg/ml- 2.5mg; Serum Estradiol Level 251-350 pg/ml- 5 mg; Serum Estradiol Level \>350 pg/ml - 7.5 mg;
|
Fixed Dose Letrozole
n=22 participants at risk
Patients who are randomized to fixed dose Letrozole will start Letrozole 5mg daily (orally) on the second day of their menstrual cycle and then gonadotropins on the fourth day of their menstrual cycle.
Letrozole: Fixed dose of 5 mg per day Letrozole will be started on the second day of their menstrual cycle.
|
|---|---|---|
|
Gastrointestinal disorders
abdominal pain
|
33.3%
6/18 • Number of events 6 • 5 years
Only 40 subjects analyzed out of 41 (1 subject was not included because they withdrew consent prior to randomization).
|
18.2%
4/22 • Number of events 4 • 5 years
Only 40 subjects analyzed out of 41 (1 subject was not included because they withdrew consent prior to randomization).
|
|
Reproductive system and breast disorders
OHSS
|
11.1%
2/18 • Number of events 2 • 5 years
Only 40 subjects analyzed out of 41 (1 subject was not included because they withdrew consent prior to randomization).
|
4.5%
1/22 • Number of events 1 • 5 years
Only 40 subjects analyzed out of 41 (1 subject was not included because they withdrew consent prior to randomization).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place