Faslodex in McCune Albright Syndrome (FMAS)

This study is ongoing, but not recruiting participants.

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

ClinicalTrials.gov Identifier:

NCT00278915

First received: January 17, 2006

Last updated: January 9, 2015

Last verified: January 2015

History of Changes

Purpose

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 (early puberty) in girls with McCune-Albright syndrome (MAS).

Condition	Intervention	Phase
Puberty, Precocious McCune-Albright Syndrome	Drug: Fulvestrant	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: familial male-limited precocious puberty McCune-Albright syndrome mucopolysaccharidosis type IV

MedlinePlus related topics: Hormones Puberty

Drug Information available for: Fulvestrant

Genetic and Rare Diseases Information Center resources: Fibrous Dysplasia McCune Albright Syndrome Osteofibrous Dysplasia Precocious Puberty

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Change in the Frequency of Annualised Days of Vaginal Bleeding [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Change in the frequency of annualised days of vaginal bleeding during the 12 month treatment period compared to the 6 month baseline period, based on a worst-case scenario calculation .i.e. missing diary card days counted as bleeding days.

Secondary Outcome Measures:

Percentage of Participants With Baseline Vaginal Bleeding Who Experienced ≥50% Reduction in the Number of Vaginal Bleeding Days [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Percentage of participants with baseline vaginal bleeding who experienced ≥50% reduction in the number of vaginal bleeding days during the 12 month treatment period compared to the 6 month baseline period.
Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding Over a 6 Month Trial Period. [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding for at least 180 consecutive days during the 12 month treatment period, based on a worst-case approach i.e. missing diary card days counted as bleeding days.
Percentage of Participants With Baseline Vaginal Bleeding Who Experienced Cessation of Vaginal Bleeding . [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Percentage of participants with baseline vaginal bleeding who experienced cessation of vaginal bleeding for the full 12 month treatment period, based on a worst-case approach i.e. missing diary card days counted as bleeding days.
Change in Bone Age Advancement Over the First 6 Month Trial Period. [ Time Frame: baseline to first 6 months of the treatment period ] [ Designated as safety issue: No ]
Change in the rate of increase in bone age from pre treatment (based on the 6 month retrospective visit) to the first 6 months of the treatment period. Bone age advancement for a particular time period was calculated as the increase in bone age over that time period adjusted (ie, normalized) for the length of that time period.
Change in Bone Age Advancement Over the Second 6 Month Trial Period. [ Time Frame: baseline to second 6 months of the treatment period. ] [ Designated as safety issue: No ]
Change in the rate of increase in bone age from pre treatment (based on the 6 month retrospective visit) to the second 6 months of the treatment period. Bone age advancement for a particular time period was calculated as the increase in bone age over that time period adjusted (ie, normalized) for the length of that time period.
Change in Bone Age Advancement Over the Whole 12 Month Trial Period. [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Change in the rate of increase in bone age from pre treatment (based on the 6 month retrospective visit) to the full 12 month treatment period. (Using last value carried forward method for the one patient who withdrew soon after their month 6 bone scan) Bone age advancement for a particular time period was calculated as the increase in bone age over that time period adjusted (ie, normalized) for the length of that time period.
Change in Growth Velocity (Annualised Growth Velocity i.e. cm/y) Over the First 6 Month Trial Period. [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 6 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Change in growth velocity (annualised growth velocity.i.e. cm/y) from the pre treatment period to the first 6 months of the treatment period. 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)
Change in Growth Velocity (Annualised Growth Velocity i.e. cm/y) Over the Second 6 Month Trial Period. [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Change in growth velocity (annualised growth velocity i.e. cm/y) from the pre treatment period to the second 6 months of the treatment period. 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)
Change in Growth Velocity (Annualised Growth Velocity i.e. cm/y) Over the Whole 12 Month Trial Period. [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Change in growth velocity (annualised growth velocity i.e. cm/y) from the pre treatment period to the full 12 month treatment period. 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)
Change in Growth Velocity (Z-Score) Over the First 6 Month Trial Period. [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 6 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Change from pre-treatment period to the first 6 months of the treatment period. Z-score is [(growth velocity from the previous visit to the current visit - mean) / standard deviation(SD)], where the mean and SD are from the National Center for Health Statistics, Fels study.
Change in Growth Velocity (Z-Score) Over the Second 6 Month Trial Period. [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Change in growth velocity (Z-Score) from pre-treatment to the second 6 months of the treatment period. Z-score is [(growth velocity from the previous visit to the current visit - mean) / standard deviation(SD)], where the mean and SD are from the National Center for Health Statistics, Fels study.
Change in Growth Velocity (Z-Score) Over the Whole 12 Month Trial Period. [ Time Frame: 6 month pre-treatment observation period (baseline) followed by 12 month treatment period (on treatment period) ] [ Designated as safety issue: No ]
Change in growth velocity (Z-Score) from pre-treatment to the full 12 month treatment period. Z-score is [(growth velocity from the previous visit to the current visit - mean) / standard deviation(SD)], where the mean and SD are from the National Center for Health Statistics, Fels study.
Change in Uterine Volume From Baseline to Month 12 by Ultrasound. [ Time Frame: Screening visit (baseline) and Month 12 during the treatment period. ] [ Designated as safety issue: No ]
Uterine volume was calculated via ultrasound using the formula: 0.5(longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated.
Change in Uterine Volume From Baseline to Month 6 by Ultrasound. [ Time Frame: Screening visit (baseline) and Month 6 during the treatment period. ] [ Designated as safety issue: No ]
Uterine volume was calculated via ultrasound using the formula: 0.5(longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated.
Change in Uterine Volume From Month 6 to Month 12 by Ultrasound. [ Time Frame: Month 6 and Month 12 during the treatment period. ] [ Designated as safety issue: No ]
Uterine volume was calculated via ultrasound using the formula: 0.5(longitudinal multiplied by anteroposterior multiplied by transverse), if all 3 linear dimensions were recorded. If all 3 linear dimensions were not recorded, uterine volume was not calculated.
Change in Ovarian Volume From Baseline to Month 12 by Ultrasound. [ Time Frame: Screening visit (baseline), Months 6 and 12 during the treatment period. ] [ Designated as safety issue: No ]
Change in Ovarian Volume From Baseline to Month 6 by Ultrasound. [ Time Frame: Screening visit (baseline), Months 6 and 12 during the treatment period. ] [ Designated as safety issue: No ]
Change in Ovarian Volume From Month 6 to Month 12 by Ultrasound. [ Time Frame: Screening visit (baseline), Months 6 and 12 during the treatment period. ] [ Designated as safety issue: No ]
Hormone Assays: Serum Oestradiol. [ Time Frame: Month 12 of the treatment period. ] [ Designated as safety issue: No ]
Hormone assays: serum oestradiol at Screening visit (baseline), Month 12 of the treatment period. Results presented relate to Month 12 of the treatment period.
Hormone Assays: Luteinizing Hormone (LH). [ Time Frame: Month 12 of the treatment period. ] [ Designated as safety issue: No ]
Hormone assays: Luteinizing hormone (LH) at Screening visit (baseline), Month 12 of the treatment period. Results presented relate to Month 12 of the treatment period.
Hormone Assays: Follicle-stimulating Hormone (FSH). [ Time Frame: Month 12 of the treatment period. ] [ Designated as safety issue: No ]
Hormone assays: follicle-stimulating hormone (FSH)at Screening visit (baseline), Month 12 of the treatment period. Results presented relate to Month 12 of the treatment period..
Hormone Assays: Testosterone. [ Time Frame: Month 12 of the treatment period. ] [ Designated as safety issue: No ]
Hormone assays: testosterone at Screening visit (baseline), Month 12 of the treatment period. Results presented relate to Month 12 of the treatment period..
PK: Mean Clearance. [ Time Frame: Throughout the 12 month treatment period. ] [ Designated as safety issue: No ]
Mean clearance is the average amount of Fulvestrant which is eliminated
PK: Mean Volume of Distribution (V1/F) [ Time Frame: Throughout the 12 month treatment period. ] [ Designated as safety issue: No ]
Total apparent volume of distribution (Vss/F) is the total apparent volume in the body into which Fulvestrant distributes at equilibrium. Vss/F = V1/F + V2/F. V1/F is the volume of the 1st compartment and V2/F is the volume of the second compartment. V1/F only is presented here. The measure of variability presented is the inter-individual error.
PK: Mean Volume of Distribution (V2/F) . [ Time Frame: Throughout the 12 month treatment period. ] [ Designated as safety issue: No ]
Total apparent volume of distribution (Vss/F) is the total apparent volume in the body into which Fulvestrant distributes at equilibrium. Vss/F = V1/F + V2/F. V1/F is the volume of the 1st compartment and V2/F is the volume of the second compartment. V2/F only is presented here. The measure of variability presented is the inter-individual error.
Change in Breast Tanner Stage From Baseline to Month 12. [ Time Frame: 6 month pre-treatment observation period (result at Month 0 considered as baseline) followed by 12 month treatment period (on treatment period). ] [ Designated as safety issue: No ]
Change in breast Tanner stage from baseline to Month 12/last visit. Tanner stage (breast) is a score of range 1-5 where 1=no development and 5=adult breast
Change in Pubic Tanner Stage From Baseline to Month 12. [ Time Frame: 6 month pre-treatment observation period (result at Month 0 considered as baseline) followed by 12 month treatment period (on treatment period). ] [ Designated as safety issue: No ]
Change in pubic Tanner stage from baseline to Month 12/last visit. Tanner stage (pubic) is a score of range 1-5 where 1=no development and 5=adult pubic hair
Change in Predicted Adult Height (PAH) From Baseline to Month 12. [ Time Frame: 6 month pre-treatment observation period (result at Screening considered as baseline) followed by 12 month treatment period (on treatment period). ] [ Designated as safety issue: No ]
Change in PAH from baseline to Month 12/final visit for patients equal to or over 6 years of age.
Percentage of Patients With Gsα Mutation. [ Time Frame: Screening assessment (baseline) ] [ Designated as safety issue: No ]
McCune-Albright Syndrome(MAS) is caused by an activating mutation in the gene coding for the stimulatory subunit of the G protein, Gsα. The altered Gsα causes autonomous activation of G-protein stimulated cAMP formation, which in the gonads, results in episodic uncontrolled sex steroid production and subsequent pubertal development. For patients who provided separate specific informed consent, the percentage of patients with a Gsα mutation at screening was assessed by molecular analysis.


Enrollment:	34
Study Start Date:	January 2006
Estimated Study Completion Date:	July 2023
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: Fulvestrant intramuscular injection Other Names: Faslodex ZD9238

Eligibility


Ages Eligible for Study:	1 Year to 10 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Females less than or equal to 10 years of age (prior to 11th birthday)
Diagnosis of McCune-Albright syndrome (MAS)
Progressive precocious puberty (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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00278915

Locations


United States, Alabama
Research Site
Birmingham, Alabama, United States
United States, Florida
Research Site
Miami, Florida, United States
United States, Kentucky
Research Site
Lexington, Kentucky, United States
United States, Louisiana
Research Site
Baton Rouge, Louisiana, United States
United States, New York
Research Site
Bronx, New York, United States
United States, Pennsylvania
Research Site
Philadelphia, Pennsylvania, United States
United States, Utah
Research Site
Salt Lake City, Utah, United States
France
Research Site
Bordeaux, France
Research Site
BRON Cedex, France
Research Site
Paris Cedex 12, France
Germany
Research Site
Erlangen, Germany
Research Site
Osnabrück, Germany
Italy
Research Site
Torino, Italy
Russian Federation
Research Site
Moscow, Russian Federation
United Kingdom
Research Site
Liverpool, United Kingdom
Research Site
London, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators


Study Director:	AstraZeneca Faslodex Medical Science Director, MD	AstraZeneca

More Information

Additional Information:

CSR-D6992C00044.pdf This link exits the ClinicalTrials.gov site

No publications provided


Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00278915 History of Changes
Other Study ID Numbers:	D6992C00044, EUDRACT Number: 2005-004893-29
Study First Received:	January 17, 2006
Results First Received:	December 6, 2010
Last Updated:	January 9, 2015
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:


Progressive Precocious Puberty PPP McCune-Albright Syndrome MAS

Additional relevant MeSH terms:


Fibrous Dysplasia, Polyostotic Fibrous Dysplasia of Bone Puberty, Precocious Syndrome Bone Diseases Bone Diseases, Developmental	Disease Endocrine System Diseases Gonadal Disorders Musculoskeletal Diseases Osteochondrodysplasias Pathologic Processes

ClinicalTrials.gov processed this record on February 27, 2015

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