Intervention: Rosiglitazone Maleate
Trial phase: Phase 2
SMILES: CN(CCOc1ccc(CC2SC(=O)NC2=O)cc1)c1ccccn1.O=C(O)C=CC(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 1
Group description: Patients receive 4 mg oral rosiglitazone maleate once daily in week 1 and then 8 mg once daily beginning in week 2 and continuing for up to 12 months in the absence of disease progression or unacceptable toxicity.

rosiglitazone maleate : Given orally
Eligibility criteria:
Inclusion Criteria:

Clinically demonstrable pituitary tumor, including either of the following subtypes:
ACTH-secreting adenoma

Residual or recurrent disease ≥ 1 month after prior pituitary surgery

Clinically demonstrable tumor, as evidenced by both of the following:

Elevated 24-hour urinary free cortisol (UFC) level
Lack of suppression of 8 a.m. serum cortisol to < 1.8 µg/dL after administration of dexamethasone 1 mg at 11 p.m. the previous night
Tumor demonstrated by MRI performed with and without contrast and/or by inferior petrosal sinus sampling with evidence of a central ACTH source.
Normal visual field evaluation by Goldman perimetry
Hypopituitarism allowed as evidenced by any or all of the following:
Subnormal growth hormone (GH) response to arginine/GH-releasing hormone testing (normal response is an increase of 2-6 ng/me)
Low age and sex-matched IGF-1 levels
Low thyroid-stimulating hormone, free triiodothyronine, and free thyroxine levels
Low estradiol levels
Low leuteinizing hormone (LH) and low follicle-stimulating hormone (FSH) levels in post-menopausal female patients OR low testosterone, LH, and FSH levels in male patients
Patients with Cushing disease (i.e., harboring ACTH-secreting pituitary adenomas) must meet the following criteria:
Hypercortisolemic (i.e., uncured) despite ≥ 1 pituitary surgery
Refuse to undergo pituitary irradiation and/or bilateral adrenalectomy
Refuse alternate steroid-lowering therapy such as ketoconazole and/or metyrapone.
Negative pregnancy test
Fertile patients must use effective contraception for at least 2 months prior to, during, and for 1 month after completion of study therapy.

Non-secreting pituitary adenoma

Newly diagnosed disease or residual tumor after prior surgical debulking

Patients underwent prior surgical debulking must be ≥ 3 months post-surgery
More than 10 mm in widest diameter (i.e., macroadenoma), as demonstrated by pituitary MRI performed with and without gadolinium
Must be able to undergo pituitary MRI (group 2)
More than 2 months since prior blood donation > 400 mL
More than 1 month since prior unlicensed drugs or participation in a clinical trial using an investigational drug
More than 3 months since prior rosiglitazone maleate or other thiazolidinedione
Patients diagnosed with hypopituitarism (except post-menopausal females) are required to initiate hormone-replacement therapy (HRT) for the 6-month duration of the study and to discontinue HRT at the end of 6 months to re-evaluate hypopituitarism

Exclusion Criteria:

Acromegaly as demonstrated by normal serum insulin-like growth factor-1 (IGF-1) level
Cushing disease as demonstrated by normal 24-hour UFC cortisol level

Prolactinoma as demonstrated by normal to moderately elevated prolactin levels (moderate elevations in serum prolactin [< 200 ng/mL] can occur in non-secreting tumors due to pituitary stalk displacement)

clinically significant renal, hematologic, cardiac, or hepatic abnormalities within the past month
other active malignancy within the past five years except basal cell carcinoma or carcinoma in situ of the cervix
evidence of drug or alcohol abuse
prior or current medical condition that may interfere with the conduct of the study or evaluation of its results, in the opinion of the Investigator or the Data Safety Monitoring Board compliance officer
postmenopausal female receiving HRT
pregnant or nursing
history of immunocompromise, including known HIV positivity as measured by enzyme-linked immunosorbent assay and western blot
active or suspected acute or chronic uncontrolled infection
history of noncompliance to medical regimens, potentially unreliability, or inability to complete the study
prior or concurrent radiotherapy for pituitary tumor
concurrent pituitary surgery