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

NCT00612066 | Terminated Phase 2 Results DMC

• 2 other identifiers: CDR0000586468UCLA-0612080-01
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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).

Conditions

Cushing's Disease

Keywords

ACTH-producing pituitary tumor

Outcome Measures

Primary Outcomes (1)

• 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).

  7 weeks

Study Arms (1)

Rosiglitazone

EXPERIMENTAL

Drug: rosiglitazone maleate

Interventions

rosiglitazone maleate DRUG

Rosiglitazone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

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

Study Sites (1)

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

MeSH Terms

Conditions

Pituitary ACTH Hypersecretion

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and 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.

Results Point of Contact

• Title: Anthony Heaney, M.D. Ph.D
• Organization: University of California, Los Angeles

aheaney@mednet.ucla.edu

310 267 4980

Study Officials

• Anthony Heaney, MD

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2008
• First Posted: February 11, 2008
• Study Start: April 1, 2007
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: August 6, 2020
• Results First Posted: February 17, 2016

Record last verified: 2016-01

Locations

US (1)