Rosiglitazone in Treating Patients With Newly Diagnosed ACTH-Secreting Pituitary Tumor (Cushing Disease)
Condition: Cushing's Disease
MeSH terms: ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion
Intervention: rosiglitazone maleate
Intervention MeSH terms: Rosiglitazone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: ACTH-producing pituitary tumor

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).
    

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