Cushing's Disease
Conditions
Keywords
ACTH-producing pituitary tumor
Brief 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).
Detailed 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.
Interventions
Sponsors
National Institutes of Health (NIH)
Jonsson Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Responders | 7 weeks | Definition of Treatment Response * The primary outcome in Cushing's disease will the % responders, a responder is defined as a patient with 2 consecutive 24h urinary free cortisols within the normal reference range in association with no clinical signs of disease progression. * Secondary outcomes will include the % reduction in 24h UFC (derived by comparison of the mean of 2 baseline 24h UFC values with mean of the two lowest consecutive 24h UFC values while on study treatment in association with no clinical signs of disease progression). |
Countries
United States
Participant flow
Recruitment details
Recruitment period May 2006-May 2009
Participants by arm
| Arm | Count |
|---|---|
| Rosiglitazone Rosiglitazone maleate : | 2 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Rosiglitazone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
Number of Responders
Definition of Treatment Response * The primary outcome in Cushing's disease will the % responders, a responder is defined as a patient with 2 consecutive 24h urinary free cortisols within the normal reference range in association with no clinical signs of disease progression. * Secondary outcomes will include the % reduction in 24h UFC (derived by comparison of the mean of 2 baseline 24h UFC values with mean of the two lowest consecutive 24h UFC values while on study treatment in association with no clinical signs of disease progression).
Time frame: 7 weeks
Population: Sample size was too small to do a valid analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rosiglitazone | Number of Responders | 1 participants |