Trial Outcomes & Findings for Aromatase Inhibitor Host Factors Study (NCT NCT01669343)

NCT ID: NCT01669343

Last Updated: 2021-05-13

Results Overview

Determine if estradiol levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed BMI

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 121 participants
• Primary outcome timeframe: Day 29
• Results posted on: 2021-05-13

Participant Flow

Participant milestones

Measure	Post-menopausal Women Using Adjuvant Letrozole Part A: All patients enrolled, on standard of care letrozole; Part B: All patients with BMI\>=25 who completed Part A, on a double dose of letrozole
Part A: All Patients STARTED	121
Part A: All Patients COMPLETED	112
Part A: All Patients NOT COMPLETED	9
Part B: Patients With BMI>=25 STARTED	48
Part B: Patients With BMI>=25 COMPLETED	31
Part B: Patients With BMI>=25 NOT COMPLETED	17

Reasons for withdrawal

Measure	Post-menopausal Women Using Adjuvant Letrozole Part A: All patients enrolled, on standard of care letrozole; Part B: All patients with BMI\>=25 who completed Part A, on a double dose of letrozole
Part A: All Patients Withdrawal by Subject	7
Part A: All Patients Ineligibility discovered after enrollment	2
Part B: Patients With BMI>=25 Withdrawal by Subject	13
Part B: Patients With BMI>=25 Recruited during interim analysis	3
Part B: Patients With BMI>=25 Ineligibility discovered after enrollment	1

Baseline Characteristics

Only overweight/obese participant who completed Part A were enrolled in Part B

Baseline characteristics by cohort

Measure	Post-menopausal Women Using Adjuvant Letrozole n=112 Participants Part A: All patients enrolled, on standard of care letrozole; Part B: All patients with BMI\>=25 who completed Part A, on a double dose of letrozole
Age, Continuous Part A	61.7 years STANDARD_DEVIATION 7.6 • n=112 Participants • Only overweight/obese participant who completed Part A were enrolled in Part B
Age, Continuous Part B	61.0 years STANDARD_DEVIATION 66 • n=31 Participants • Only overweight/obese participant who completed Part A were enrolled in Part B
Sex: Female, Male Part A · Female	112 Participants n=112 Participants • Only overweight/obese participant who completed Part A were enrolled in Part B
Sex: Female, Male Part A · Male	0 Participants n=112 Participants • Only overweight/obese participant who completed Part A were enrolled in Part B
Sex: Female, Male Part B · Female	31 Participants n=31 Participants • Only overweight/obese participant who completed Part A were enrolled in Part B
Sex: Female, Male Part B · Male	0 Participants n=31 Participants • Only overweight/obese participant who completed Part A were enrolled in Part B
Age at menopause Part A	49.2 years STANDARD_DEVIATION 4.7 • n=112 Participants • Only overweight/obese participant who completed Part A were enrolled in Part B
Age at menopause Part B	48.4 years STANDARD_DEVIATION 5.2 • n=31 Participants • Only overweight/obese participant who completed Part A were enrolled in Part B
Vitamin D supplementation Part A	109 Participants n=112 Participants • Only overweight/obese participant who completed Part A were enrolled in Part B
Vitamin D supplementation Part B	31 Participants n=31 Participants • Only overweight/obese participant who completed Part A were enrolled in Part B
Letrozole use prior to study	18.1 months STANDARD_DEVIATION 17.6 • n=112 Participants

PRIMARY outcome

Timeframe: Day 29

Population: Part A

Determine if estradiol levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed BMI

Outcome measures

Measure

Post-menopausal Women Using Adjuvant Letrozole n=112 Participants Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.

Part A Correlation of Day 29 Estradiol With BMI

0.06 correlation coefficient Interval -0.13 to 0.24

PRIMARY outcome

Timeframe: Day 29

Population: Part A

Determine if estrone levels vary with BMI levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed BMI

Outcome measures

Measure

Post-menopausal Women Using Adjuvant Letrozole n=112 Participants Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.

Part A Correlation of Day 29 Estrone With BMI

0.07 correlation coefficient Interval -0.12 to 0.25

PRIMARY outcome

Timeframe: Day 29

Population: Part A

Determine if estradiol levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estradiol and log-transformed Vitamin D level

Outcome measures

Measure

Post-menopausal Women Using Adjuvant Letrozole n=112 Participants Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.

Part A Correlation of Day 29 Estradiol With Vitamin D

-0.04 correlation coefficient Interval -0.22 to 0.15

PRIMARY outcome

Timeframe: Day 29

Population: Part A

Determine if estrone levels vary with Vitamin D levels levels after 28 days of monitored adherence to standard dose letrozole, by calculating the Pearson correlation between estrone and log-transformed Vitamin D level

Outcome measures

Measure

Post-menopausal Women Using Adjuvant Letrozole n=112 Participants Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.

Part A Correlation of Day 29 Estrone With Vitamin D

0.04 correlation coefficient Interval -0.14 to 0.23

PRIMARY outcome

Timeframe: Day 29 to Day 58

Population: Part B participants

In overweight/obese patients enrolled in part B, determine if blood levels of estradiol levels changed from before to after the double dose of letrozole

Outcome measures

Measure

Post-menopausal Women Using Adjuvant Letrozole n=31 Participants Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.

Part B Change in Estradiol Level After Double Dose of Letrozole

0.1 pmol/L Interval -0.56 to 0.78

SECONDARY outcome

Timeframe: Day 29 and day 58

Population: Data were not collected

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline, day 29 (end of part A)

Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life

Outcome measures

Measure	Post-menopausal Women Using Adjuvant Letrozole n=112 Participants Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.
Endocrine Symptoms During Part A of Study Day 1	62.4 score on a scale Standard Deviation 9.6
Endocrine Symptoms During Part A of Study Day 29	62.9 score on a scale Standard Deviation 10.4

SECONDARY outcome

Timeframe: day 29 (end of part A) and day 58 (end of part B)

Functional Assessment of Cancer Therapy - Endocrine Sub-scale (FACT-ES) consists of 19 questions answered of a Likert scale. The sub-scale score ranges from 0 to 76 and the higher the score the better the quality of life

Outcome measures

Measure	Post-menopausal Women Using Adjuvant Letrozole n=31 Participants Part A Routine Care Letrozole; Part B Double Dose Letrozole in overweight/obese participants Letrozole: Part A Monitor standard of care letrozole use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period. Part B In overweight/obese participants who completed Part A, provide a double dose of letrozole and monitor use for 28 days; measure blood levels of estrogens and vitamin D at start and end of period.
Endocrine Symptoms During Part B of the Study Day 29	61.7 score on a scale Standard Deviation 11.1
Endocrine Symptoms During Part B of the Study Day 58	61.2 score on a scale Standard Deviation 11.5

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline (day 1), day 29 (end of part A) and day 58 (end of part B)

Outcome measures

Outcome data not reported

Adverse Events

Full Study

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Full Study n=121 participants at risk Adverse events collected during part A, 29 days of monitored adherence to standard of care letrozole and Part B .
Renal and urinary disorders Renal Colic/Constipation	0.83% 1/121 • Number of events 1 • Adverse events were collected over the duration of the study: 29 days for patients taking part in Part A only, 58 days for patients that took part in Parts A and B National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.01
Vascular disorders Stroke	0.83% 1/121 • Number of events 1 • Adverse events were collected over the duration of the study: 29 days for patients taking part in Part A only, 58 days for patients that took part in Parts A and B National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.01

Other adverse events

Measure	Full Study n=121 participants at risk Adverse events collected during part A, 29 days of monitored adherence to standard of care letrozole and Part B .
Musculoskeletal and connective tissue disorders Arthralgia	6.6% 8/121 • Number of events 8 • Adverse events were collected over the duration of the study: 29 days for patients taking part in Part A only, 58 days for patients that took part in Parts A and B National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.01

Additional Information

Dr. David Cescon

Princess Margaret Hospital

Phone: 416-946-2000

Email: dave.cescon@uhn.on.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place