Clinical trial NCT00278915: Faslodex in McCune-Albright Syndrome
Official title: An Open-label, Non-Comparative Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Faslodex (Fulvestrant) in Girls With Progressive Precocious Puberty Associated With McCune-Albright Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Puberty, Precocious
McCune-Albright Syndrome
Keywords: Progressive Precocious Puberty
PPP
McCune-Albright Syndrome
MAS
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2006-01-19
Enrollment: 30
Sex: FEMALE
Minimum age (years): 1
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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)


Eligibility criteria: Inclusion Criteria:

* Females less than or equal to 10 years of age (prior to 11th birthday)
* Diagnosis of MAS
* PPP associated with MAS

Exclusion Criteria:

* Received any prior treatment for PPP associated with MAS with fulvestrant
* Abnormal platelet count or liver function tests
* Bleeding disorders
* Long term anticoagulation therapy
* Known hypersensitivity to any component of the study drug

Primary outcomes:
measure: Change in Frequency of Annualized Days of Vaginal Bleeding on Treatment Compared to Baseline
timeFrame: Baseline (6 month pre-treatment observation period) through Month 12 treatment period
measure: Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥ 50% Reduction in the Number of Vaginal Bleeding Days on Treatment Compared to Baseline
timeFrame: Baseline (6 month pre-treatment observation period) through Month 12 treatment period
measure: Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6-month Treatment Period
timeFrame: Baseline (6-month pre-treatment observation period) through Month 12 treatment period
measure: Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over the Whole 12-month Treatment Period
timeFrame: Baseline (6 month pre-treatment observation period) through Month 12 treatment period
measure: Change in Rate of Bone Age (BA) Advancement Over First 6-month Treatment Period Compared to Baseline
timeFrame: Baseline (6-month pre-treatment observation period) through Month 6 of treatment period
measure: Change in Rate of BA Advancement Over Second 6-month Treatment Period Compared to Baseline
timeFrame: Baseline (6-month pre-treatment observation period) through second Month 6 of treatment period
measure: Change in Rate of BA Advancement Over the Whole 12-month Treatment Period Compared to Baseline
timeFrame: Baseline (6-month pre-treatment observation period) through Month 12 of treatment period
measure: Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over First 6-month Treatment Period Compared to Baseline
timeFrame: Baseline (6 month pre-treatment observation period) through first 6-month of treatment period
measure: Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over Second 6-month Treatment Period Compared to Baseline
timeFrame: Baseline (6 month pre-treatment observation period) through second 6-month treatment period (ie, through 12-month treatment period)
measure: Change in Growth Velocity (Annualized Growth Velocity in cm/Year) Over Whole 12-month Treatment Period Compared to Baseline
timeFrame: Baseline (6 month pre-treatment observation period) through Month 12 of treatment period
measure: Change in Growth Velocity (Z-score) Over the First 6-month Treatment Period Compared to Baseline
timeFrame: Baseline (6 month pre-treatment observation period) through first 6-month treatment period
measure: Change in Growth Velocity (Z-score) Over the Second 6-month Treatment Period Compared to Baseline
timeFrame: Baseline (6 month pre-treatment observation period) through second 6-month treatment period
measure: Change in Growth Velocity (Z-score) Over the Whole 12-month Treatment Period Compared to Baseline
timeFrame: Baseline (6 month pre-treatment observation period) through Month 12 of treatment period
measure: Change in Uterine Volume From Baseline to Month 6 as Assessed by Ultrasound
timeFrame: Baseline (pre-treatment baseline visit) and Month 6 of treatment period
measure: Change in Uterine Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound
timeFrame: At Month 6 and Month 12/final visit treatment period
measure: Change in Uterine Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound
timeFrame: Baseline (pre-treatment screening visit) and Month 12 treatment period
measure: Change in Mean Ovarian Volume From Baseline to Month 6 as Assessed by Ultrasound
timeFrame: Baseline (pre-treatment screening visit) and Month 6 of treatment period
measure: Change Mean in Ovarian Volume From Month 6 to Month 12/Final Visit as Assessed by Ultrasound
timeFrame: At Month 6 and Month 12/final visit treatment period
measure: Change in Mean Ovarian Volume From Baseline to Month 12/Final Visit as Assessed by Ultrasound
timeFrame: Baseline (pre-treatment baseline visit) and Month 12/final visit treatment period
measure: Mean Clearance of Fulvestrant
timeFrame: Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose
measure: Mean Volume of Distribution (V1/F) of Fulvestrant
timeFrame: Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose
measure: Mean Volume of Distribution (V2/F) of Fulvestrant
timeFrame: Post-dose: Weeks 1, 2, 3, and pre-dose: Week 4 of Month 1 for first 6 participants, then pre-dose steady state samples on 2 occasions between Months 6 and 12 with at least 1 month in between wherein first sample drawn at least 30 days following sixth dose
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through 68.7 weeks (maximum observed duration)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
timeFrame: Day 1 through 68.7 weeks (maximum observed duration)
measure: Number of Participants With Compliance to Study Treatment
timeFrame: Day 1 through Month 12 of treatment period
measure: Number of Participants With Withdrawals From Study Treatment Due to TEAE
timeFrame: Day 1 through 68.7 weeks (maximum observed duration)
measure: Hormone Assay: Serum Oestradiol Level
timeFrame: Month 12 (final visit) of treatment period
measure: Hormone Assay: Serum Luteinizing Hormone (LH) Level
timeFrame: Month 12 (final visit) of treatment period
measure: Hormone Assay: Serum Follicle-stimulating Hormone (FSH) Level
timeFrame: Month 12 (final visit) of treatment period
measure: Hormone Assay: Serum Testosterone Level
timeFrame: Month 12 (final visit) of treatment period
Secondary outcomes:
measure: Change in Tanner Stage of Breast From Baseline to Month 12/Final Visit
timeFrame: From Baseline (Month 0) through Month 12 treatment period
measure: Change in Tanner Stage of Pubic Hair From Baseline to Month 12/Final Visit
timeFrame: From Baseline (Month 0) through Month 12 treatment period
measure: Change in Predicted Adult Height (PAH) From Baseline to Month 12/Final Visit
timeFrame: From Baseline (screening visit) through Month 12 treatment period
measure: Percentage of Participants With McCune-Albright Syndrome (MAS) Associated G Protein α-subunit (Gsα) Mutation
timeFrame: Baseline (screening)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Miami
country: United States
facility: Research Site
state: Florida
city: Lexington
country: United States
facility: Research Site
state: Kentucky
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: Bronx
country: United States
facility: Research Site
state: New York
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Bordeaux
country: France
facility: Research Site
city: Bron
country: France
facility: Research Site
city: Paris Cedex 12
country: France
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Osnabrück
country: Germany
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Faslodex Medical Science Director, MD
role: STUDY_DIRECTOR
References:
citation: Sims EK, Garnett S, Guzman F, Paris F, Sultan C, Eugster EA; Fulvestrant McCune-Albright study group. Fulvestrant treatment of precocious puberty in girls with McCune-Albright syndrome. Int J Pediatr Endocrinol. 2012 Sep 22;2012(1):26. doi: 10.1186/1687-9856-2012-26.