Clinical trial NCT00612066: Rosiglitazone in Treating Patients With Newly Diagnosed ACTH-Secreting Pituitary Tumor (Cushing Disease)
Official title: An Open Label, Multicenter Study Evaluating the Safety and Efficacy of Short Term (6 Weeks) Rosiglitazone Treatment in Patient's With Cushing's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cushing's Disease
Keywords: ACTH-producing pituitary tumor
Lead sponsor: Jonsson Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2008-02-11
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Rosiglitazone may help pituitary tumor cells become more like normal cells, and to grow and spread more slowly.

PURPOSE: This phase II trial is studying how well rosiglitazone works in treating patients with newly diagnosed ACTH-secreting pituitary tumor (Cushing disease).

Detailed description: OBJECTIVES:

Primary

* To assess the effect of rosiglitazone on biochemical control in patients with newly diagnosed ACTH-secreting pituitary tumor (Cushing disease).

Secondary

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

Eligibility 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 triiodothyronine (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.

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

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

Primary outcomes:
measure: Number of Responders
timeFrame: 7 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: Anthony Heaney, MD
role: PRINCIPAL_INVESTIGATOR
References: