NCT00278915: FMAS

Faslodex in McCune-Albright Syndrome

Completed Phase 2 Results posted Last updated 5 March 2024

What this trial tests

Phase 2 trial testing Fulvestrant in Puberty, Precocious in 30 participants. Completed in 20 July 2023.

Timeline

31 January 2006

Primary endpoint
8 December 2009

20 July 2023

Quick facts

Lead sponsor	AstraZeneca
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	30
Start date	31 January 2006
Primary completion	8 December 2009
Estimated completion	20 July 2023
Sites	16 locations across France, Italy, Russia, United Kingdom, Germany, United States

Drugs / interventions tested

• Fulvestrant (fulvestrant) — full drug profile →

Conditions studied

• Puberty, Precocious — all drugs for Puberty, Precocious →
• McCune-Albright Syndrome — all drugs for McCune-Albright Syndrome →

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 1 to 10, female only, with Puberty, Precocious or McCune-Albright Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Frequency of Annualized Days of Vaginal Bleeding on Treatment Compared to Baseline Primary · Baseline (6 month pre-treatment observation period) through Month 12 treatment period

Vaginal bleeding days are defined as the number of days in which vaginal bleeding, (including spotting) occurred. In order to annualize, a 12-month period is defined as 360 days and a 6-month period is defined as 180 days. Frequency of annualized vaginal bleeding days = \[(number of vaginal bleeding days)/(total number of days of the time interval under consideration)\] multiplied by 360. Change in frequency is equal to the on-treatment frequency minus the baseline frequency. Diary cards will capture days of vaginal bleeding during the 12-month treatment period. Change in the frequency of annu

Group	Value	95% CI
Fulvestrant	-3.6	-42 – 185

Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥ 50% Reduction in the Number of Vaginal Bleeding Days on Treatment Compared to Baseline Primary · Baseline (6 month pre-treatment observation period) through Month 12 treatment period

The percentage change in frequency is defined as 100% times the difference (the on-treatment period frequency minus the baseline period frequency), divided by the baseline period frequency. The percentage of participants with baseline vaginal bleeding days who experienced ≥ 50% reduction in the number of vaginal bleeding days during the 12 month treatment period compared to the 6 month baseline period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.

Group	Value	95% CI
Fulvestrant	73.9	51.6 – 89.8

Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6-month Treatment Period Primary · Baseline (6-month pre-treatment observation period) through Month 12 treatment period

Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding days over a 6-month treatment period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.

Group	Value	95% CI
Fulvestrant	78.3	56.3 – 92.5

Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over the Whole 12-month Treatment Period Primary · Baseline (6 month pre-treatment observation period) through Month 12 treatment period

Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding days over a 12-month treatment period based on a worst-case approach (ie, missing diary card days counted as bleeding days) are reported.

Group	Value	95% CI
Fulvestrant	34.8	16.4 – 57.3

Change in Rate of Bone Age (BA) Advancement Over First 6-month Treatment Period Compared to Baseline Primary · Baseline (6-month pre-treatment observation period) through Month 6 of treatment period

Change in rate of BA advancement over first 6-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in chronological age (CA) (years). Change in rate of increase in BA from baseline period

Group	Value	95% CI
Fulvestrant	-0.83	± 1.507

Change in Rate of BA Advancement Over Second 6-month Treatment Period Compared to Baseline Primary · Baseline (6-month pre-treatment observation period) through second Month 6 of treatment period

Change in rate of BA advancement over second 6-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in CA (years). Change in rate of increase in BA from baseline period to on-treatment per

Group	Value	95% CI
Fulvestrant	-1.10	± 1.383

Change in Rate of BA Advancement Over the Whole 12-month Treatment Period Compared to Baseline Primary · Baseline (6-month pre-treatment observation period) through Month 12 of treatment period

Change in rate of BA advancement over whole 12-month treatment period compared to baseline (6-month pre-treatment observation period) is reported. Increase in BA is defined as BA (expressed as fractional years) at end of time period minus BA at beginning of time period (unit: years). Rate of increase in BA for a particular time interval is increase in BA during this time interval adjusted (ie, normalized) for the length of this time interval. Rate of BA advancement is change in BA (years) divided by change in CA (years). Change in rate of increase in BA from baseline period to on-treatment per

Group	Value	95% CI
Fulvestrant	-0.93	± 1.343

Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over First 6-month Treatment Period Compared to Baseline Primary · Baseline (6 month pre-treatment observation period) through first 6-month of treatment period

Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to first 6-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.

Group	Value	95% CI
Fulvestrant	-1.7	± 4.35

Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over Second 6-month Treatment Period Compared to Baseline Primary · Baseline (6 month pre-treatment observation period) through second 6-month treatment period (ie, through 12-month treatment period)

Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to second 6-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.

Group	Value	95% CI
Fulvestrant	-0.8	± 4.49

Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over Whole 12-month Treatment Period Compared to Baseline Primary · Baseline (6 month pre-treatment observation period) through Month 12 of treatment period

Change in growth velocity (annualized growth velocity in cm/year) from the baseline (pre-treatment period) to the 12-month treatment period is reported. Growth velocity for a particular time period was calculated as the increase in height over that time period divided by the length of that time period (expressed in cm/year). Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Change in growth velocity was calculated as growth velocity on treatment minus change in growth velocity during baseline.

Group	Value	95% CI
Fulvestrant	-1.4	± 3.69

Change in Growth Velocity (Z-score) Over the First 6-month Treatment Period Compared to Baseline Primary · Baseline (6 month pre-treatment observation period) through first 6-month treatment period

Change in growth velocity (Z-score) from baseline period to the first 6 months of treatment period is reported. The Z-score (also known as Standard Deviation Score \[SDS\]) is defined as \[(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by standard deviation (SD)\], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the st

Group	Value	95% CI
Fulvestrant	-1.60	± 4.616

Change in Growth Velocity (Z-score) Over the Second 6-month Treatment Period Compared to Baseline Primary · Baseline (6 month pre-treatment observation period) through second 6-month treatment period

Change in growth velocity (Z-score) from baseline period to the second 6 months of treatment period is reported. The Z-score (also known as SDS) is defined as \[(growth velocity from the previous visit to the current visit minus mean growth velocity) divided by SD\], where the mean and SD are the age- and gender-specific statistics for growth velocity from the National Center for Health Statistics, Fels study and age is the age at the current visit. Baseline growth velocity was calculated from 6-month observational/retrospective period of the study. Z-score of 0 represents the population mean

Group	Value	95% CI
Fulvestrant	-0.64	± 4.606

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 through 68.7 weeks (maximum observed duration). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Fulvestrant

Serious: 9/30 (30%)

Deaths: 0/30

Serious adverse events (13 terms)

Reaction	System	Fulvestrant
Pyrexia	General disorders	—
Bronchitis	Infections and infestations	—
Viral Infection	Infections and infestations	—
Femur Fracture	Injury, poisoning and procedural complications	—
Dehydration	Metabolism and nutrition disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Bone Pain	Musculoskeletal and connective tissue disorders	—
Pain In Extremity	Musculoskeletal and connective tissue disorders	—
Dizziness	Nervous system disorders	—
Neuromyopathy	Nervous system disorders	—
Tic	Psychiatric disorders	—
Ovarian Cyst	Reproductive system and breast disorders	—
Wheezing	Respiratory, thoracic and mediastinal disorders	—

Other adverse events (40 terms — click to expand)

Reaction	System	Fulvestrant
Pyrexia	General disorders	—
Abdominal Pain	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Headache	Nervous system disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Rhinitis	Infections and infestations	—
Diarrhoea	Gastrointestinal disorders	—
Upper Respiratory Tract Infection	Infections and infestations	—
Pain In Extremity	Musculoskeletal and connective tissue disorders	—
Injection Site Inflammation	General disorders	—
Abdominal Pain Upper	Gastrointestinal disorders	—
Oropharyngeal Pain	Respiratory, thoracic and mediastinal disorders	—
Ear Pain	Ear and labyrinth disorders	—
Nasopharyngitis	Infections and infestations	—
Toothache	Gastrointestinal disorders	—
Ear Infection	Infections and infestations	—
Gastroenteritis	Infections and infestations	—
Tonsillitis	Infections and infestations	—
Urinary Tract Infection	Infections and infestations	—
Decreased Appetite	Metabolism and nutrition disorders	—
Rash	Skin and subcutaneous tissue disorders	—
Fatigue	General disorders	—
Injection Site Pain	General disorders	—
Nausea	Gastrointestinal disorders	—
Lethargy	Nervous system disorders	—
Bronchitis	Infections and infestations	—
Otitis Media	Infections and infestations	—
Pharyngitis	Infections and infestations	—
Pharyngitis Streptococcal	Infections and infestations	—
Sinusitis	Infections and infestations	—
H1N1 Influenza	Infections and infestations	—
Vaginal Infection	Infections and infestations	—
Varicella	Infections and infestations	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Bone Pain	Musculoskeletal and connective tissue disorders	—
Neck Pain	Musculoskeletal and connective tissue disorders	—
Eczema	Skin and subcutaneous tissue disorders	—
Productive Cough	Respiratory, thoracic and mediastinal disorders	—
Hot Flush	Vascular disorders	—
Injection Site Reaction	General disorders	—

Most-reported serious reactions: Pyrexia, Bronchitis, Viral Infection, Femur Fracture, Dehydration, Arthralgia, Bone Pain, Pain In Extremity.

Data from ClinicalTrials.gov NCT00278915 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the safety, effectiveness and pharmacokinetics of a study drug called Faslodex (fulvestrant) in the treatment of progressive precocious puberty (PPP) (early puberty) in girls with McCune-Albright syndrome (MAS)

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Fulvestrant treatment of precocious puberty in girls with McCune-Albright syndrome.
   Sims EK, Garnett S, Guzman F, Paris F, et al · · 2012 · cited 16× · PMID 22999294 · DOI 10.1186/1687-9856-2012-26