Rosiglitazone in Treating Patients With Newly Diagnosed ACTH-Secreting Pituitary Tumor (Cushing Disease)

• Sponsor: Jonsson Comprehensive Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00612066
• Collaborator: National Institutes of Health (NIH) (NIH)
• Enrollment: 2
• Location: 1
• Arm: 1
• Duration (Months): 43
• Patients Per Site Per Month: 0

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Cushing's Disease	Drug: rosiglitazone maleate	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label, Multicenter Study Evaluating the Safety and Efficacy of Short Term (6 Weeks) Rosiglitazone Treatment in Patient's With Cushing's Disease
• Study Start Date: Apr 1, 2007
• Actual Primary Completion Date: Nov 1, 2010
• Actual Study Completion Date: Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rosiglitazone	Drug: rosiglitazone maleate

Outcome Measures

Primary Outcome Measures

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781

Sponsors and Collaborators

• Jonsson Comprehensive Cancer Center
• National Institutes of Health (NIH)

Investigators

• Principal Investigator: Anthony Heaney, MD, Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonsson Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00612066
• Other Study ID Numbers: CDR0000586468; UCLA-0612080-01
• First Posted: Feb 11, 2008
• Last Update Posted: Aug 6, 2020
• Last Verified: Jan 1, 2016

• Keywords provided by Jonsson Comprehensive Cancer Center: ACTH-producing pituitary tumor
• Additional relevant MeSH terms: ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion; Rosiglitazone

Study Results

Participant Flow

Recruitment Details	Recruitment period May 2006-May 2009

Arm/Group Title	Rosiglitazone
Arm/Group Description	Rosiglitazone maleate :
Period Title: Overall Study
STARTED	2
COMPLETED	1
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Rosiglitazone
Arm/Group Description	Rosiglitazone maleate :
Overall Participants	2
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	2 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 50%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	1 50%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Responders
Description	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

Outcome Measure Data

Analysis Population Description

Sample size was too small to do a valid analysis.

Arm/Group Title	Rosiglitazone
Arm/Group Description	Rosiglitazone maleate :
Measure Participants	1
Number [participants]	1 50%

Adverse Events

Arm/Group Title	Rosiglitazone
Arm/Group Description	Rosiglitazone maleate :
All Cause Mortality
	Rosiglitazone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rosiglitazone
	Affected / at Risk (%)	# Events
Total	0/2 (0%)
Other (Not Including Serious) Adverse Events
	Rosiglitazone
	Affected / at Risk (%)	# Events
Total	1/2 (50%)
General disorders
edema in limbs	1/2 (50%)	1

Limitations/Caveats

Recruitment was a major limitation. Patients were available but were not interested in the study due to possible side effects of the study drug.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.