Pediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis]

Study Overview
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Brief Summary
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The primary objective of this study is to investigate whether bicalutamide given in combination with anastrozole once daily for 12 months is effective in treating testotoxicosis in boys. Testotoxicosis is a condition that causes early puberty in boys including growth in height, and development of muscles and sexual organs .

Official Title
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An Open-label, Non-comparative, Multi-centre Study to Assess the Efficacy and Safety of Bicalutamide When Used in Combination With Anastrozole for the Treatment of Gonadotropin-independent Precocious Puberty in Boys With Testotoxicosis

Conditions
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Puberty, Precocious

Intervention / Treatment
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* Drug: Bicalutamide
* Drug: Anastrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of written informed consent of parent/legal guardian and subject assent (as needed by local requirements) Male aged 2 years and over Diagnosis of testotoxicosis based on the following: Clinical features of Progressive sexual precocity documented by Tanner staging and evidence of symmetrical testicular enlargement Clinical features of significantly advanced bone age (defined as bone age of at least 12 months beyond chronological age) Pubertal levels of serum testosterone Prepubertal levels of serum gonadotropins Lack of an increase in serum gonadotropin levels following GnRH stimulation Other pathology excluded by: Undetectable plasma b human chorionic gonadotropin (bHCG). Samples with values below the LOQ will be reported as <10 IU/L which in the clinical setting equate to 'undetectable'. Normal levels of 17-hydroxyprogesterone (17-OHP) Normal levels of dehydroepiandrosterone sulphate (DHEAS) Naive to anti androgen receptor therapy: (Note: Ketoconazole and Spironolactone are considered acceptable as is prior use of anastrozole or other aromatase inhibitors) A documented reliable height measurement taken > 6 months prior to study enrollment. Additionally for subjects who have previously received ketoconazole or spironolactone treatment, a documented reliable height measurement taken immediately prior to beginning this treatment. (Note: for subjects who received such previous treatment only a single assessment is needed if it was taken immediately prior to beginning treatment and > 6 months prior to study entry) Subjects should be free of endocrine or other effects of previous treatment for testotoxicosis prior to study entry: to ensure this there should be 15 days or 4 drug half lives (whichever is the longer) washout period from prior medication for testotoxicosis. Exclusion Criteria: Evidence of central precocious puberty as demonstrated by GnRH stimulation test Serum concentration of total or direct bilirubin, GGT, AST or ALT greater than 1.5 times the upper limit of normal for age Serum concentration of creatinine greater than 1.5 times the upper limit of normal for age Any concomitant medical condition that, in the opinion of the investigator, may expose a subject to an unacceptable level of safety risk or that affects subject compliance Known hypersensitivity to any of the study medications Participation in a clinical study at the time of enrollment

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 13 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Bicalutamide with Anastrozole<br>Bicalutamide in combination with Anastrozole | Drug: Bicalutamide<br>* oral<br>* Other names: Casodex;Drug: Anastrozole<br>* oral<br>* Other names: ZD1033;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Growth Rate (cm/Year) | Change in growth rate after 12 months relative to the growth rate during the ≥6 month pre-study period, based on raw height data (cm/year). | Assessed after 12 months treatment | 
| Change in Growth Rate (SD Units) | Change in growth rate after 12 months relative to the growth rate during the ≥6 month pre-study period, calculated after adjustment for the chronological age of the patient (expressed as a standard deviation [SD] score). | Assessed after 12 months treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Growth Rate (cm/Year) | Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period. | Assessed after 6 months treatment | 
| Change in Growth Rate (SD Units) | Change in growth rate after 6 months of treatment relative to the growth rate during the ≥6 months pre-study period. | Assessed after 6 months treatment | 
| Change in Bone Age Maturation Rate (cm/Year) | Radiographs were used to assess the bone age at ≥6 months pre-study, baseline, 6 and 12 months. The rate of change in bone age at baseline was calculated from a radiograph taken at least 6 months prior to study enrolment. The change in bone maturation after 6 months of treatment was calculated relative to the rate of change in bone age during the ≥ 6 months pre-study period. | Assessed after 6 and 12 months treatment | 
| Change in Bone Age to Chronological Age Ratio | Change in bone age to chronological age ratio after 6 and 12 months treatment relative to the baseline ratio for all patients. | Assessed after 6 and 12 months of treatment | 
| Number of Patients With Height Between 5th and 95th Percentile | The number of patients whose height lies between the 5th and 95th percentiles (using the percentile tables on the WHO database) for chronological age at the 12 month assessment. | Assessed after 3, 6, 9 and 12 months of treatment | 
| Change in Predicted Adult Height (PAH) | Radiographs are used to assess the bone age, the change in predicted adult height (PAH) is calculated from the bone age using the Bayley and Pinneau Method. The change in PAH is be calculated by subtracting the PAH at baseline from the PAH at 12 months. | Assessed after 12 months treatment | 
| Change in Average Testicular Volume | Testicular volume of both testes was measured using either ultrasound or an orchidometer. Testicular volume was measured at baseline and at 6 and 12 months. The change in testicular volume from baseline was calculated for the left and right testicle as well as the average across both testes by subtracting the baseline volume from the volumes at 6 and 12 months within each patient. | Assessed after 6 and 12 months of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Testotoxicosis, Familial Male-limited Precocious Puberty (FMPP)