Rosiglitazone in Treating Patients With Pituitary Tumors
Condition: Brain and Central Nervous System Tumors
MeSH terms: Nervous System Neoplasms; Central Nervous System Neoplasms; Pituitary Neoplasms; Pituitary Diseases
Intervention: rosiglitazone maleate
Intervention description: Given orally
Intervention MeSH terms: Rosiglitazone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: recurrent pituitary tumor; ACTH-producing pituitary tumor; nonfunctioning pituitary tumor

Summary:

      RATIONALE: Rosiglitazone may help pituitary adenoma cells become more like normal cells, and
      grow and spread more slowly.

      PURPOSE: This phase II trial is studying how well rosiglitazone works in treating patients
      with newly diagnosed or residual or recurrent pituitary adenoma.
    

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