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Rosiglitazone (Peroxisome Proliferating Activating Receptor-gamma {PPAR-y} Ligand) Treatment of Pituitary Tumors


Phase 2
18 Years
65 Years
Not Enrolling
Both
Brain and Central Nervous System Tumors

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Trial Information

Rosiglitazone (Peroxisome Proliferating Activating Receptor-gamma {PPAR-y} Ligand) Treatment of Pituitary Tumors


OBJECTIVES:

- To assess the effect of rosiglitazone maleate on the core biochemical parameter,
24-hour urinary free cortisol levels, in patients with recurrent or uncured
pituitary-dependent Cushing disease. (Group 1)

- To assess the effect of this drug on corticotropin-releasing hormone-stimulated
pituitary tumor ACTH secretion in patients with recurrent or uncured
pituitary-dependent Cushing disease. (Group 1)

- To assess the effect of this drug on tumor growth in patients with non-secreting
pituitary macroadenoma (> 10 mm) using RECIST criteria. (Group 2)

- To assess the effect of this drug on pituitary tumor gonadotropin (i.e.,
follicle-stimulating hormone, leuteinizing hormone, and alpha-subunit) secretion in
patients with non-secreting macroadenoma. (Group 2)

- To assess the overall safety and tolerability of this drug in both cohorts of patients.

- To assess the overall quality of life, in terms of performance status during treatment,
of both cohorts of patients using the Karnofsky performance index.

OUTLINE: Patients are grouped according to adrenocorticotropic hormone (ACTH)-secreting
status (yes [Group 1] vs no [Group 2]).

- Group 1 (ACTH-secreting adenomas): 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 6 months in the absence of disease progression or unacceptable toxicity.

- Group 2 (non-secreting macroadenomas): 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.

Patients undergo collection of blood and urine samples at baseline and after completion of
study therapy to assess pituitary function, thyroid function, and 24-hour urinary free
cortisol levels. Additional assessments include corticotrophin-stimulation testing, dynamic
pituitary function testing (i.e., arginine/growth-hormone releasing-hormone testing) to
measure growth hormone secretion, and overnight 1 mg dexamethasone suppression testing to
measure 8 a.m. serum cortisol levels. Patients also undergo MRI at baseline and after
completion of study therapy to examine the effects of rosiglitazone maleate treatment on
pituitary tumor size.

Patients complete a questionnaire at baseline and monthly during study for evaluation of
headaches.

PROJECTED ACCRUAL: A total of 15 patients with ACTH-secreting pituitary tumor and 15
patients with non-secreting pituitary macroadenomas will be accrued for this study.


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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Efficacy of Rosiglitazone Maleate on Cushing Disease

Outcome Description:

Reduction in pituitary tumor volume by over 50% as assessed by MRI to measurements made at baseline.

Outcome Time Frame:

12 months

Safety Issue:

No

Principal Investigator

Anthony Heaney, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jonsson Comprehensive Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000586480

NCT ID:

NCT00616642

Start Date:

October 2006

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • recurrent pituitary tumor
  • ACTH-producing pituitary tumor
  • nonfunctioning pituitary tumor
  • Nervous System Neoplasms
  • Pituitary Neoplasms
  • Central Nervous System Neoplasms

Name

Location

Jonsson Comprehensive Cancer Center at UCLALos Angeles, California  90095-1781