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

Jonsson Comprehensive Cancer Center

Status and phase

Terminated

Phase 2

Conditions

Cushing's Disease

Treatments

Drug: rosiglitazone maleate

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00612066

UCLA-0612080-01

CDR0000586468

Details and patient eligibility

About

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).

Full 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.

Enrollment

2 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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