Multicenter Study of Seliciclib (R-roscovitine) for Cushing Disease

NCT03774446 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: Pro52406FD-R-6106
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 2 multicenter, open-label clinical trial will evaluate safety and efficacy of 4 weeks of oral seliciclib in patients with newly diagnosed, persistent, or recurrent Cushing disease. Funding Source - FDA Office of Orphan Products Development (OOPD)

Conditions

Cushing Disease

Keywords

Cushing disease; R-roscovitine; Seliciclib

Outcome Measures

Primary Outcomes (2)

• Number of participants with a normalized 24-hour urinary free cortisol (UFC) at study completion

  4 weeks

• Number of participants with UFC above the upper limit of normal (ULN) but reduced by ≥50% from baseline at study completion

  4 weeks

Secondary Outcomes (11)

• Plasma adrenocorticotrophic hormone

  Baseline and week 4

• Salivary cortisol

  Baseline and week 4

• Serum cortisol

  Baseline and week 4

• Glycated hemoglobin (HbA1c)

  Baseline and week 4

• Fasting blood glucose

  Baseline and week 4

Study Arms (1)

Seliciclib

EXPERIMENTAL

80 mg each day oral seliciclib for 4 weeks

Drug: Seliciclib

Interventions

Seliciclib DRUG

Drug: Seliciclib

Also known as: R-roscotivine

Seliciclib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients at least 18 years old
• Patients with confirmed pituitary origin of excess adrenocorticotropic hormone (ACTH) production:
• Persistent hypercortisolemia established by two consecutive 24-hour UFC assessment ≥1.5× the upper limit of normal
• Normal or elevated ACTH levels
• Pituitary adenoma (\>1 cm) on MRI or inferior petrosal sinus sampling (IPSS) central to peripheral ACTH gradient \>2 at baseline and \>3 after CRH stimulation
• Recurrent or persistent CD defined as pathologically confirmed resected pituitary ACTH-secreting tumor or IPSS central to peripheral ACTH gradient \>2 at baseline and \>3 after CRH stimulation, and 24h-UFC \>ULN beyond post-surgical week 6
• Patients on medical treatment for Cushing disease. The following washout periods must be completed before screening assessments are performed:
• Inhibitors of steroidogenesis: metyrapone, ketoconazole: 2 weeks; Levoketoconazole: 3 weeks; osilodrostat: 6 weeks
• Somatostatin receptor ligand pasireotide: short-acting, 2 weeks; long-acting, 4 weeks
• Progesterone receptor antagonist mifepristone: 2 weeks
• Dopamine agonist cabergoline: 4 weeks
• Patients treated with CYP3A or CYP2B6 strong inducers or inhibitors, including those listed below. Required washout time varies between drugs; minimum 5-6 times the half-life of the drug.
• Strong CYP3A inducers: apalutamide, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort
• Moderate CYP3A inducers: bosentan, efavirenz, etravirine, phenobarbital, primidone
• Weak CYP3A inducers: armodafinil, modafinil, rufinamide

You may not qualify if:

• Patients with compromised visual fields, and not stable for at least 6 months
• Patients with abutment or compression of the optic chiasm on MRI and normal visual fields
• Patients with Cushing's syndrome due to non-pituitary ACTH secretion
• Patients with hypercortisolism secondary to adrenal tumors or nodular (primary) bilateral adrenal hyperplasia
• Patients who have a known inherited syndrome as the cause for hormone over secretion (i.e., Carney Complex, McCune-Albright syndrome, Multiple endocrine neoplasia (MEN) 1
• Patients with a diagnosis of glucocorticoid-remedial aldosteronism (GRA)
• Patients with cyclic Cushing's syndrome defined by any measurement of UFC over the previous 1 months within normal range
• Patients with pseudo-Cushing's syndrome, i.e., non-autonomous hypercortisolism due to overactivation of the hypothalamic-pituitary-adrenal (HPA) axis in uncontrolled depression, anxiety, obsessive compulsive disorder, morbid obesity, alcoholism, and uncontrolled diabetes mellitus
• Patients who have undergone major surgery within 1 month prior to screening
• Patients with serum K+\< 3.5 while on replacement treatment
• Diabetic patients whose blood glucose is poorly controlled as evidenced by HbA1C \>8%
• Patients who have clinically significant impairment in cardiovascular function or are at risk thereof, as evidenced by congestive heart failure (NYHA Class III or IV), unstable angina, sustained ventricular tachycardia, clinically significant bradycardia, high grade atrioventricular (AV) block, history of acute MI less than one year prior to study entry
• Patients with liver disease or history of liver disease such as cirrhosis, chronic active hepatitis B and C, or chronic persistent hepatitis, or patients with abnormal alanine transferase (ALT) or aspartate aminotransferase (AST) at screening or patients with advanced liver fibrosis (≥10 kPa) on elastography at screening
• Patients with estimated glomerular filtration rate (eGFR) \<45 mL/min/1.73 m2
• Patients not biochemically euthyroid

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Related Publications (2)

• Liu NA, Araki T, Cuevas-Ramos D, Hong J, Ben-Shlomo A, Tone Y, Tone M, Melmed S. Cyclin E-Mediated Human Proopiomelanocortin Regulation as a Therapeutic Target for Cushing Disease. J Clin Endocrinol Metab. 2015 Jul;100(7):2557-64. doi: 10.1210/jc.2015-1606. Epub 2015 May 5.

  PMID: 25942479 BACKGROUND

• Liu NA, Jiang H, Ben-Shlomo A, Wawrowsky K, Fan XM, Lin S, Melmed S. Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor. Proc Natl Acad Sci U S A. 2011 May 17;108(20):8414-9. doi: 10.1073/pnas.1018091108. Epub 2011 May 2.

  PMID: 21536883 BACKGROUND

MeSH Terms

Conditions

Pituitary ACTH Hypersecretion

Interventions

Roscovitine

Condition Hierarchy (Ancestors)

Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Shlomo Melmed, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

• Ning-Ai Liu, MD, PhD

  Cedars-Sinai Medical Center

  STUDY DIRECTOR

Central Study Contacts

Daniel Gomez

CONTACT

424-315-2362; grouppituitaryresearch@cshs.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sr. Vice President of Academic Affairs

Study Record Dates

• First Submitted: November 6, 2018
• First Posted: December 13, 2018
• Study Start: November 2, 2018
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: September 11, 2025

Record last verified: 2025-09

Locations

US (1)