Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Rosiglitazone in Treating Patients With Newly Diagnosed ACTH-Secreting Pituitary Tumor (Cushing Disease)

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Active	18 to 65	NCI	UCLA-0612080-01 06-12-080-01, NCT00612066

Objectives

Primary

1. To assess the effect of rosiglitazone on biochemical control in patients with newly diagnosed ACTH-secreting pituitary tumor (Cushing disease).
2. To assess the effect of this drug on a core biochemical parameter (24-hour urinary-free cortisol) associated with disease progression.

Secondary

1. To assess the effect of this drug on corticotrophin (CRH)-stimulated pituitary tumor ACTH secretion.
2. To assess the overall safety and tolerability of this drug in these patients.
3. To assess the overall quality of life of patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Clinically demonstrable ACTH-secreting pituitary tumor
  • Pituitary tumor demonstrated on MRI with and without contrast AND/OR evidence of a central ACTH source following inferior petrosal sinus sampling
  • Newly diagnosed disease



• Biochemically active disease that is not adequately controlled, as demonstrated by the following standard criteria:
  • Elevated 24-hour urinary-free cortisol levels on at least 2 separate 24-hour urine collections 1 week apart
  • Lack of suppression of serum cortisol to < 1.8 μg/dL (at 8 am) following administration of 1 mg of dexamethasone at 11 pm the night before
  • Measurable plasma ACTH levels



• Patient is hypercortisolemic and does not wish to receive alternate steroid-lowering therapy, such as ketoconazole and/or metyrapone



• Patients with evidence of optic nerve or chiasm compression on post-operative MRI must have a normal visual field evaluation by Goldman perimetry
  • No visual field abnormalities



• Hypopituitarism* allowed, as evidenced by any or all of the following:
  • Subnormal growth hormone (GH) response to arginine/growth hormone-releasing hormone (GHRH) testing (normal response is an increase of > 4 ng/mL)
  • Low age-and sex-matched insulin-like growth factor-1 (IGF-1) levels
  • Low thyroid-stimulating hormone (TSH) levels
  • Low free triodothyronine (T3) and free thyroxine (T4) levels
  • Low estradiol levels
  • Low luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in postmenopausal female patients
  • Low testosterone, LH, and FSH levels in male patients

   [Note: *Patients who are diagnosed with hypopituitarism will initiate thyroid hormone replacement therapy prior to pituitary surgery as part of routine care. Other hormone replacement, such as sex steroids or growth hormone, will not be initiated during the study.]

Prior/Concurrent Therapy:

• More than 3 months since prior rosiglitazone or other thiazolidinedione
• No prior or concurrent radiotherapy for pituitary tumor
• More than 1 month since prior participation in any clinical investigation involving an investigational drug
• More than 30 days since prior unlicensed drugs
• No concurrent pituitary surgery

Patient Characteristics:

• Not pregnant or nursing
• Fertile patients must use effective contraception (if oral contraception is used, it must be used for ≥ 2 months prior to, during, and for 1 month after completion of study therapy)
• No clinically significant renal, hematologic, or hepatic abnormalities
• No prior or concurrent medical condition that may interfere with the conduct of the study or the evaluation of its results, in the opinion of the investigator or the DSMB compliance officer
• No history of immunocompromise, including HIV positivity by ELISA and western blot
• No alcohol or drug abuse within the past 6 months
• No blood donation (≥ 400 mL) within the past 2 months
• No other active malignant disease within the past 5 years except for basal cell carcinoma or carcinoma in situ of the cervix
• No active or suspected acute or chronic uncontrolled infection
• No severe osteoporosis, defined as bone mineral density T scores < 2.5 standard deviations below age-matched controls
• No history of noncompliance to medical regimens
• Considered reliable
• Able to complete the entire study

Expected Enrollment

Outcomes

Percentage of responders

Percentage of reduction in 24-hour urinary-free cortisol levels

Outline

This is a multicenter study.

Patients receive oral rosiglitazone once daily for 7 weeks in the absence of disease progression or unacceptable toxicity.

Blood, urine, and saliva samples are collected periodically for laboratory studies. Inflammatory markers (C-reactive protein, interleukin-6 [IL-6], serum sialic acid, soluble intracellular and vascular adhesion molecules [sICAM-1, and sVCAM-1], and amyloid A) are measured at baseline and at the completion of study treatment; salivary cortisol and 24-hour urinary-free cortisol levels are measured at baseline and weekly during study treatment; dexamethasone suppression tests with serum cortisol and corticotrophin (CRH) stimulation test are performed at baseline and at the completion of study treatment; prolactin, insulin-like growth factor-1 (IGF1), thyroid function, and sex steroid hormones are measured at baseline and at the completion of study treatment; and dynamic pituitary function testing (arginine/growth hormone-releasing hormone [GHRH] testing to measure growth hormone secretion) is performed at baseline.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Anthony Heaney, MD, Principal investigator		Ph: 310-825-5874; 888-798-0719

U.S.A.
California
	Los Angeles
	Jonsson Comprehensive Cancer Center at UCLA
		Clinical Trials Office - Jonsson Comprehensive Cancer Center at UCLA	Ph:  888-798-0719

Registry Information
Official Title		An open label, multicenter study evaluating the safety and efficacy of short term (6 weeks) Rosilgitazone treatment in patient's with Cushing's Disease
Trial Start Date		2007-04-05
Trial Completion Date		2009-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00612066
Date Submitted to PDQ		2008-01-25
Information Last Verified		2008-08-08
NCI Grant/Contract Number		CA16042