Neoplasms

Nervous System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

ACTH-Secreting Pituitary Adenoma

Pituitary ACTH Hypersecretion

Adenoma

Pituitary Diseases

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pituitary Neoplasms

Endocrine Gland Neoplasms

ACTH-secreting Pituitary Adenoma

Anti-Inflammatory Agents

All Drugs and Chemicals

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Hydrocortisone

Hydrocortisone 17-butyrate 21-propionate

Hydrocortisone acetate

Hydrocortisone hemisuccinate

Dexamethasone

Dexamethasone acetate

Cortisone

Patients with Cushing Disease (CD) receiving a medical treatment: n = 30 Plasmatic cortisol UFC Urine biocollection Salive biocollection

Patient group

Patients in remission of CD and having recovered a normal pituitary function for at least 12 months following pituitary surgery (normal UFC associated to: cortisol suppression following dexamethasone suppression test, or normal LNSC, or midnight serum cortisol \< 200 nmol/L) n = 15 Plasmatic cortisol UFC Urine biocollection Salive biocollection Haircortisol

Remission control group

Patients with previous CD, treated with bilateral adrenalectomy and receiving weight adjusted doses of hydrocortisone for at least 6 months. Last daily dose of Hydrocortisone should be administered no later than 5 pm. n = 15 Plasmatic cortisol UFC Urine biocollection Salive biocollection Haircortisol

Bilateral surrenalectomy control group

Antoine TABARIN, Pr

The biochemical tools usable to assess the control of hypercortisolism in patients with Cushing's disease receiving medical treatments are debatable. The aim of the study is to compare the results of the measurement of cortisol and cortisone using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in scalp hair (so called "Hair Cortisol") to that of 24h urinary free cortisol (UFC) and late night salivary cortisol (LNSC) for the monitoring of medical therapy in patients with Cushing's disease (CD).

Selective surgical removal of the pituitary corticotroph adenoma is the ideal treatment of Cushing's disease. However, surgery may not be feasible or is unsuccessful in roughly 25% of patients. In addition, a recurrence of the disease is observed after a transient remission in 15 to 25% of patients. Several therapeutic alternatives are available, amongst which medical treatment is commonly used. Drugs that are available in France to control hypercortisolism target the pituitary adenoma secretion (pasireotide and cabergoline) or inhibit adrenal steroidogenesis (ketoconazole and metyrapone). Usual criteria to monitor the treatment and titrate the drug dosage include evaluation of relevant clinical endpoints and measurement of UFC. However, limitations of UFC for this purpose, include difficulties in obtaining a complete 24 urine collection and the fact that UFC assess only short-term cortisol in a disease characterized by high variability over time in the intensity of hypercortisolism. Elsewhere, a mild to moderate hypercortisolism may persist despite a normal UFC. Several groups, including ours, have shown that LNSC is useful tool to diagnose overt and mild hypercortisolism and may be more sensitive than UFC to diagnose mild hypercortisolism. Despite being more convenient to collect than 24h urine, LNSC also suffers from only measuring time-point cortisol. Rare studies have examined whether LNSC could be an adequate biomarker for monitoring response to medical therapy in patients with CD and its usefulness to monitor drug treatment in CD is yet unknown (one study comparing UFC to LNSC in CD patients treated with pasireotide-LAR has been presented but is not yet published). Accordingly, the 2015 guidelines of the endocrine society recommend future research to accurately monitor patients for their response to medical therapy to guide dose optimization. More recently, the measurement of salivary cortisone in 3 saliva samples (SCx3) drawn at approximately 8 hours intervals and starting at 7-8 am have been shown to be a reliable estimate of cortisol production over 24h in normal subjects. Whether this parameter could be used as a substitute of UFC in patients treated with anticortisolic drugs remains unstudied.

Hair cortisol concentration is a non-invasive way to measure cortisol exposure over much longer periods of time (weeks and months) than previously possible with samples of blood, saliva or urine. Several studies have shown that measurement of cortisol in a single scalp hair sample has a diagnostic accuracy for CS similar to currently used first-line tests and may also be used to identify overtreatment in patients receiving hydrocortisone replacement for adrenal insufficiency. To date, no data is available concerning hair Cortisol measurement in comparison with other usual biological tools in patients with CD receiving a medical treatment.

Since 2016, the departments of endocrine biology and clinical endocrinology of Bordeaux university hospital (CHU) have developed the measurement of cortisol and cortisone in scalp hair using LC-MS/MS and have established normative values using several cohorts of control patients.

The purpose of the study is to take advantage of the ability of hair cortisol to measure long-term cortisol exposure to assess the response to medical therapy in patients with CD. More specifically, the working hypothesis is that some patients with a normal UFC may still suffer from an occult mild hypercortisolism that will be identified only by hair cortisol. To study this hypothesis, the investigators will compare the results of hair cortisol to that multiple measurement of UFC, LNSC and SCx3 during a three-month period in patients with CD already treated with medical treatments and considered as "controlled" on the basis of previous UFC measurements.

Hair Cortisol and Cushing's Disease

Usefulness of Hair Cortisol/Cortisone Concentrations for the Monitoring of Medical Treatment in Patients With Cushing's Disease

Hypercortisolism will be controlled using 3 cm scalp hair sample in which Hair Cortisol will be measured in patients with Cushing Disease (CD) receiving a medical treatment.

Compare Hair Cortisol to UFC (Urinary Free Cortisol), LNSC (late night salivary cortisol) and SC (salivary cortisone) in patients with CD receiving a medical treatment.

Compare the results of Hair Cortisol measurements in patients with CD receiving a medical treatment and patients treated with weight-adjusted hydrocortisone replacement doses after bilateral adrenalectomy

Compare the results of Hair Cortisol measurements in patients cured from CD and patients with bilateral adrenalectomy

Evaluate the dosage of within-patient variability of Hair Cortisol for patients with CD receiving a medical treatment and control groups : patients cured from CD and patients with bilateral adrenalectomy

Assess the within-patient variability of UFC in patients with CD receiving a medical treatment

Correlate a quality of life assessment with the results of Hair Cortisol, UFC and LNSC thanks to QOL questionnaire : cushing's QOL.

Evaluate the dosage of within-patient variability of LNSC in patients with CD receiving a medical treatment

Evaluate the dosage of within-patient variability of SC in patients with CD receiving a medical treatment

University Hospital, Bordeaux

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Central Nervous System Stimulants

Analgesics

Reproductive Control Agents

Bone Density Conservation Agents

Anti-Infective Agents

Everolimus

Megestrol

Megestrol Acetate

Sorafenib

Diphosphonates

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the investigational drug. In addition to taking Everolimus, all patients also received BSC as per normal local practice.

Placebo Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placeb Everolimus, all patients also received BSC as per normal local practice.

Everolimus (labeled as RAD001) was formulated as tablets of 2.5 mg strength and blisterpacked in units of 10 tablets.

Everolimus Placebo matched to the everolimus 2.5 mg tablet strength was blister-packed in units of 10 tablets. Matching placebo tablets were formulated to be indistinguishable from the everolimus tablets. Everolimus placebo was taken as a daily oral dose of 7.5 mg and was defined as the control drug.

Everolimus Placebo

BSC was defined as drug or non-drug therapies, nutritional support, physical therapy or anything that the Investigator believed to be in the patient's best interest, but excluding other antineoplastic treatments. BSC administered to the patient throughout the study was to be reported on the Concomitant Medication/Significant Non-Drug Therapy electronic case report from (eCRF). Permitted BSC treatments during the study included, but were not limited to, the following: Pain medication to allow the patient to be as comfortable as possible, Bisphosphonates for bone metastases, Localized radiotherapy, for the treatment of pre-existing, painful bone metastases, Nutritional support or appetite stimulants (i.e. megestrol) as recommended by the Investigator, Oxygen therapy and blood products or transfusions

Best Supportive Care (BSC)

Novartis Pharmaceuticals

The purpose of this study is to compare treatment with RAD001 plus best supportive care (BSC) to placebo plus BSC in patients with advanced HCC whose disease progressed while on or after sorafenib treatment or who are intolerant to sorafenib.

Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma.

A Randomized Phase III, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy and Safety of Everolimus (RAD001) in Adult Patients With Advanced Hepatocellular Carcinoma After Failure of Sorafenib Treatment - The EVOLVE-1 Study

OS was defined as the time from the date of randomization to the date of death from any cause. The comparison of OS between the 2 arms was done using a stratified log-rank test at one-sided 2.5% level of significance.

TTP was defined as the time from the date of randomization to the date of the first documented radiologic confirmation of disease progression. Since the study did not meet the primary objective, TTP was not formally tested.

DCR is defined as the proportion of participants with a best objective response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) according to RECIST. The BOR was the best response recorded from the start of the treatment until disease progression. CR is disappearance of all target lesions; PR is at least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. PD is at least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.

Change in Eastern Cooperative Oncology Group (ECOG) were assessed by time to definitive performance status deterioration by at least one category on the ECOG scale. Deterioration was considered definitive if no improvement in the ECOG PS was observed at a subsequent measurement. ECOG PS: 0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2=Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; 5=Dead

The primary quality of life endpoint was the time to definitive 5% deterioration from baseline in the global health status/quality of life scale of the EORTC QLQ-C30 questionnaire. Definitive deterioration by at least 5% is defined as a decrease in score by at least 5% compared to baseline, with no later observed increase above this threshold. The EORTC quality of life questionnaire (QLQ) is an integrated system for assessing the healthrelated quality of life (QoL) of cancer patients participating in international clinical trials. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

Cmin is the pre-dose blood concentration at steady-state (ng/mL). Pre-dose (Cmin) blood samples were collected from all patients in both arms at Visit 3. Steady-state for the Cmin sample was defined as continuous administration of the same dose in the last 4 days prior to the collection of the Cmin sample. Steady-state for the 5 mg every other day regimen was defined as the state when the 5 mg dose was taken 2 days and 4 days before sampling. PK samples were only drawn at visit 3, and only analyzed for patients receiving everolimus at steady state (if patients had received the dose the previous 4 days). In addition summary statistics were only done for each everolimus dose when 3 samples were available. Only valid pre-dose (Cmin) everolimus samples were included in the analysis.

Cmax is the maximum (peak) blood drug concentration after dose administration (ng/mL) calculated as the maximum of C1h and C2h. C1h was 1 hour post-dose blood concentration (ng/mL) and C2h was 2 hour post-dose blood concentration (ng/mL). C1h and C2h post-dose samples were collected from all patients in both arms at Visit 3. Steady-state for the C1h and C2h samples was defined as continuous administration of the same dose in the previous 4 days and the day on which the C1h and C2h samples were collected. Steady-state for the 5 mg every other day regimen was defined as the state when the 5 mg dose was taken 2 days and 4 days before sampling. PK samples were only drawn at visit 3, and only analyzed for patients receiving everolimus at steady state (if patients had received the dose the previous 4 days). In addition summary statistics were only done for each everolimus dose when 3 samples were available. Only valid C1h and C2h everolimus samples were included in the analysis.

Three patients (1 in the everolimus arm and 2 in the placebo arm) were excluded from the Safety Set as these patients were randomized but never received any study treatment.

Patients were assigned to the Everolimus + BSC arm in a ratio of 2:1 over the Placebo arm. Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed. In addition to taking Everolimus, all patients also received BSC as per normal local practice.

Everolimus + Best Supportive Care (BSC)

Placebo-Everolimus was taken as a daily oral dose of 7.5 mg and was defined as the control drug. In addition to taking Placebo Everolimus, all patients also received BSC as per normal local practice.

Placebo + Best Supportive Care

Total

Age, Continuous

< 35 years

>=35 - <55 years

>=55 - <65 years

>= 65 years

Age, Customized

Sex: Female, Male

Caucasian

Black

Asian

Pacific Islander

Other

Race/Ethnicity, Customized

Weight

Height

Three patients (1 in the everolimus arm and 2 in the placebo arm were excluded from the Safety Set. These three patients were randomized but never received any study treatment.

Study Director

The Full Analysis Set (FAS) comprised all randomized patients.

Overall Survival (OS)

Time to Tumor Progression (TTP)

Percentage of Participants With Disease Control Rate (DCR)

Time to Definitive Deterioration of ECOG Performance Score (PS) Score

Time to Definitive Deterioration of EORTC QLQ-C30 Scores

Everolimus 7.5mg + Best Supportive Care (BSC)

Everolimus was taken as a daily oral dose of 7.5 mg but dose adjustments of study drug (reduction, interruption or possible dose re-escalation to starting dose) according to safety findings were allowed.

Everolimus 5mg + Best Supportive Care (BSC)

Safety Set consisted of all patients who received at least one dose of study treatment with a valid postbaseline assessment. All PK analyses were based on the Safety Set.

Pharmacokinetics Assessments - Cmin

Safety Set consists of all patients who received at least one dose of study treatment with a valid postbaseline assessment. All PK analyses were based on the Safety Set.

Pharmacokinetics Assessments - Cmax

Overall Study

RAD001

RAD001, sorafenib

Phase 1 Evaluate the safety and tolerability of RAD001 in combination with sorafenib in patients with advance hepatocellular cancer (HCC) and to determine the maximum tolerated dose (MTD)

Phase 2 To estimate the treatment effect as a measure of anti-tumor activity in terms of Time to Progression (TTP) of the combination of RAD001 plus sorafenib, at the MTD, as compared to sorafenib alone

Global Study Looking at the Combination of RAD001 and Sorafenib to Treat Patients With Advanced Hepatocellular Carcinoma

A Phase 1 Open Label/ Phase 2 Randomized, Double-blind, Multicenter Study Investigating the Combination of RAD001 and Sorafenib (Nexavar®) in Patients With Advanced Hepatocellular Carcinoma

Skin and Connective Tissue Diseases

Symptoms and General Pathology

Ganglion Cysts

Headache

Post-Dural Puncture Headache

Synovial Cyst

Cysts

Pain

Neurologic Manifestations

Mucinoses

Connective Tissue Diseases

Neoplasm Metastasis

Headache Disorders

Headache Disorders, Secondary

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

Antirheumatic Agents

Lidocaine

Diclofenac

Patients will receive paracetamol 1 gm every 6 hours daily intravenously for a day.

Patients will receive sphenopalatine block

Sphenopalatine Ganglion Block will be performed by a transnasal approach. Few drops of lidocaine 2% will be instilled into both anterior nares. Then a cotton-tipped applicator soaked in 4% lignocaine \& adrenaline (1 to 200000 will be passed through both the nares and the end of the applicator tip will be positioned just superior to the middle turbinate and anterior to the pterygopalatine fossa and sphenopalatine ganglion for 5 min with the patient in the supine position.

Sphenopalatine Ganglion Block

Patients will receive paracetamol 1 gm 6 hours daily intravenously for a day. If adequate pain relief will not be achieved, intravenous diclofenac 75 mg twice daily will be added.

Medical Treatment

The aim of this study is to assess the efficacy, onset and duration of analgesia of sphenopalatine ganglion bock (SPGB) using lidocaine 4% with adrenaline as a treatment of postoperative Post dural puncture headache (PDPH) of orthopedic patients after lower limbs surgeries.

Sphenopalatine Ganglion Block for Post-Dural Puncture Headache in Orthopedic Patients

Sphenopalatine Ganglion Block With Adrenaline Additive for Post-Dural Puncture Headache in Orthopedic Patients: A Randomized Controlled Study

The data will be available upon reasonable request

Efficacy of analgesia demonstrated by visual analogue scale (VAS) less than 4 (effective) in the first 48 hours.

VAS ranges from 0 to 10; 10 with worse outcome

Local anesthetic toxicity, hypertension, postoperative epistaxis, cheek hematoma and hypoesthesia of the palate

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hair Cortisol and Cushing's Disease	NCT04201444	Cushing Disease	Patient group Remission contr... Bilateral surre...	18 Years -	University Hospital, Bordeaux
Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma.	NCT01035229	Carcinoma	Everolimus Everolimus Plac... Best Supportive...	18 Years -	Novartis
Global Study Looking at the Combination of RAD001 Plus Best Supportive Care (BSC) and Placebo Plus BSC to Treat Patients With Advanced Hepatocellular Carcinoma.	NCT01035229	Carcinoma	Everolimus Everolimus Plac... Best Supportive...	18 Years -	Novartis
Hair Cortisol and Cushing's Disease	NCT04201444	Cushing Disease	Patient group Remission contr... Bilateral surre...	18 Years -	University Hospital, Bordeaux
Global Study Looking at the Combination of RAD001 and Sorafenib to Treat Patients With Advanced Hepatocellular Carcinoma	NCT00828594	Hepatocellular ...	RAD001 RAD001, sorafen...	18 Years -	Novartis
Sphenopalatine Ganglion Block for Post-Dural Puncture Headache in Orthopedic Patients	NCT04657952	Sphenopalatine ... Adrenaline Post-Dural Punc... Orthopedic Randomized Cont...	Sphenopalatine ... Medical Treatme...	18 Years - 60 Years	Tanta University

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