Progressive precocious puberty associated with McCune-Albright Syndrome
Conditions
Interventions
Product Name: Faslodex
Product Code: ZD9238
Pharmaceutical Form: Solution for injection
INN or Proposed INN: fulvestrant
CAS Number: 129453-61-8
Current Sponsor code: ZD9238
Other descriptive name: IC
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of written informed consent of parent/legal guardian and subject assent (as required by local law) 2. For patients consenting to participate in the genetic portion of the study, provision of an additional written informed consent specific for DNA sampling and genetic analysis. 3. Females less than or equal to 10 years of age (prior to 11th birthday) at the start of trial therapy (Visit 0). 4. Diagnosis of McCune-Albright Syndrome based on having the following clinical criteria: · Precocious puberty evident before the age of 8 years And at least one of the following clinical criteria: · Café au lait spots · Fibrous dysplasia · Presence of Gsa mutation 5. Progressive precocious puberty associated with MAS. Progressive precocious puberty will be defined as: o An increase of at least one in the breast Tanner Stage over the observation period and/or o The development or persistence of vaginal bleeding during the observation period. 6. At least one of the following two criteria must also be fulfilled: o Advanced bone age: defined as, bone age of at least 12 months beyond chronological age at the time of screening. o Rapid growth rate: a growth rate over the observation period that is more than 2 standard deviations above the mean for age, where the growth rate is defined as the change in height (or length) (in cm) divided by the change in time (annualized in years). 7. Patients are eligible provided they are in one of the following categories: o Received no previous treatment and have documented retrospective data of at least 6 months for bone age, Tanner Stage, height, weight, and vaginal bleeding (number of bleeding days). o Received no previous treatment and do not have documented retrospective data of at least 6 months for bone age, Tanner Stage, height, weight and vaginal bleeding (number of bleeding days) and can be observed for 6 months without treatment (i.e., 6-month observation period). o Documented progression on treatment with anastrozole, tamoxifen, testolactone, or other aromatase inhibitors, an anti-androgen, or a progestin requiring immediate treatment provided there exists retrospective data of at least 6 months for bone age, Tanner Stage, height, weight, and vaginal bleeding (number of bleeding days) and are off these agents for 1 month prior to first dose of study drug. o Previously treated with any drug for PPP in which therapy was stopped for at least 6 months with subsequent clinical evidence of progression of disease meeting entry criteria No. 5 and 6 and retrospective data of at least 6 months for bone age, Tanner Stage, height, weight, and vaginal bleeding (number of bleeding days). 8. If central precocious puberty (CPP) exists, the patient must have been on a GnRH analog (e.g., Lupron) for at least 6 months prior to study enrollment (date of written consent of parent/legal guardian and patient assent). Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Male gender 2. Any prior treatment of PPP associated with MAS with fulvestrant 3. Concomitant treatment of PPP associated with MAS, with the exception of bisphosphonates for fibrous dysplasia and GnRH analogs in the case of CPP 4. Liver function tests (AST, ALT) at screening ³ 3´ the upper limit of the reference range for age 5. Platelet count at screening less than 100 ´ 109/L 6. International normalized ratio (INR) greater than 1.6. 7. History of bleeding diathesis or long-term anticoagulant therapy (other than antiplatelet therapy) 8. Any severe concomitant condition that makes it undesirable for the patient to participate in this study 9. Known hypersensitivity to any component of the study drug product
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Secondary objectives include assessments of pubertal progression through Tanner Staging and predicted adult height (PAH) for children over age six. The presence of a MAS associated Gsa mutation will be assessed by molecular analysis provided separate specific consent is obtained. No other genetic analysis will be performed with these specimens. The participation of patients and investigative sites in this analysis will be voluntary and any individual patient or site decision not to participate will not exclude them from this clinical study.;Primary end point(s): (a)Tolerability and safety, including adverse events, withdrawals and laboratory data (b)Change in frequency of annualized days of vaginal bleeding on treatment compared to baseline (c)Proportion of patients with baseline vaginal bleeding who experienced ³50% reduction in the number of vaginal bleeding days on treatment compared to baseline (d)Proportion of patients with baseline vaginal bleeding who experienced cessation of vaginal bleeding over a 6-month trial period and over the entire 12-month trial. (e)Change in bone age advancement (rate of increase in bone age) over a 6-month trial period and over the entire 12-month trial on treatment compared to baseline (f)Change in growth rate over a 6-month trial period and over the entire 12-month trial on treatment compared to baseline PK variables for the population PK analysis will include area under the concentration-time curve (AUC), maximum and minimum plasma concentration (Cmax and Cmin, respectively), half-life (T1/2), clearance (CL/F) and apparent volume of distribution (Vss). The effects of demographic covariates (e.g., age, body weight, race) on fulvestrant PK will also be explored. ;Main Objective: The primary objective of the trial is composed of two components: A safety and efficacy component and a pharmacokinetics (PK) component. All patients fulfilling the eligibility criteria will participate in both components of t | — |
Countries
Germany, Italy, Spain, United Kingdom
Outcome results
None listed