Treatment of Cushing's Disease With R-roscovitine

Phase 2

Terminated

Conditions: Cushings Disease

Interventions: Drug: R-roscovitine

Registration Number: NCT02160730

Lead Sponsor: Shlomo Melmed, MD

Brief Summary: The investigators hypothesize that R-roscovitine will suppress pituitary corticotroph tumor ACTH production and normalize urinary free cortisol levels in patients with Cushing disease. To date, R-roscovitine has been evaluated in several Phase I and II studies and has shown early signs of anti-cancer activity in approximately 240 patients.

Detailed Description: To date, R-roscovitine (seliciclib) has been evaluated in several Phase I and II studies and has shown early signs of anti-cancer activity in approximately 240 patients. Studies included a Phase I study in which single agent seliciclib was administered to patients with advanced non-small cell lung cancer (NSCLC) and two Phase IIa studies in which seliciclib was administered in combination with gemcitabine and cisplatin as first-line treatment and with docetaxel as second-line treatment in NSCLC. Seliciclib was also evaluated in a Phase I study in patients with nasopharyngeal cancer (NPC) with evidence of tumor shrinkage and concomitant reduction in copy counts of the EBV virus that is causally associated with the pathogenesis of NPC. Results from APPRAISE, a randomized discontinuation, double-blinded, placebo-controlled, Phase IIb study of oral seliciclib capsules as a monotherapy in heavily pretreated patients with NSCLC, demonstrated no difference between the seliciclib and placebo arms in progression free survival but a substantial increase in overall survival was observed (388 versus 218 days respectively (Cyclacel Pharmaceuticals press release Dec 21, 2010). Here, the investigators propose an exploratory, proof of concept clinical trial to determine if seliciclib can safely normalize urinary free cortisol levels by reducing pituitary corticotroph tumor ACTH production in patients with Cushing disease.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
R-roscovitine	R-roscovitine	• R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks.

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Normalized 24 Hour Urinary Free Cortisol After 4 Weeks	Baseline, 4 weeks	To evaluate the efficacy of R-roscovitine 400 mg oral administration twice daily for 4 days every week for total of 4 weeks on normalizing 24 hour urinary free cortisol (24 h UFC) levels in CD patients. "Normalizing" is defined as having urine free cortisol levels within the normal range for that lab value.

Secondary Outcome Measures

Name	Time	Method
Change in Mean HbA1c Levels Between Baseline and 4 Weeks	Baseline, 4 Weeks	HbA1c levels are measured at baseline and at study end, these are averaged across all subjects.
Number of Participants With Adverse Events	Baseline, 4 weeks	The number of participants that experience an adverse event between baseline and study end likely related to study drug as a measure of safety and tolerability.
Number of Participants That Have a Visible Change in Tumor Size	Baseline, 4 weeks	A visible change in tumor size as determined by the investigator after reviewing MRI reports between baseline and 4 weeks of treatment.
Number of Participants That Experience Changes in Clinical Signs of Hypercortisolemia	Baseline, Week 4	The number of participants that achieved a urinary free cortisol level above the upper limit of the normal range but reduced by ≥50% from baseline at week 4.
Fasting Glucose at Baseline and 4 Weeks	Baseline, 4 Weeks	Mean change between baseline and week 4 of fasting blood glucose levels.
Plasma ACTH at Baseline and 4 Weeks	Baseline, 4 weeks	Mean change in Plasma ACTH between baseline and 4 weeks.
Change in Clinical Symptoms	Baseline, 4 weeks	Change in typical Cushing's syndrome clinical signs and symptoms defined by mean weight at baseline and 4 weeks.
Changes in Serum Cortisol Between Baseline and 4 Weeks	Baseline, 4 weeks	Mean serum cortisol values at baseline and 4 weeks
Change in Systolic Blood Pressure	Baseline, 4 weeks	Mean change in systolic blood pressure between baseline and 4 weeks.
Change in Diastolic Blood Pressure	Baseline, 4 weeks	Mean diastolic blood pressure between baseline and 4 weeks.