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Rosiglitazone in Treating Patients With Pituitary Tumors

Primary Purpose

Brain and Central Nervous System Tumors

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
rosiglitazone maleate
Sponsored by
Jonsson Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring recurrent pituitary tumor, ACTH-producing pituitary tumor, nonfunctioning pituitary tumor

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Jonsson Comprehensive Cancer Center at UCLA

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group 1 (ACTH-secreting adenomas)

Group 2 (non-secreting macroadenomas)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Efficacy of Rosiglitazone Maleate on Cushing Disease
Reduction in pituitary tumor volume by over 50% as assessed by MRI to measurements made at baseline.

Secondary Outcome Measures

Full Information

First Posted
February 14, 2008
Last Updated
August 5, 2020
Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT00616642
Brief Title
Rosiglitazone in Treating Patients With Pituitary Tumors
Official Title
Rosiglitazone (Peroxisome Proliferating Activating Receptor-gamma {PPAR-y} Ligand) Treatment of Pituitary Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Terminated
Why Stopped
low patient recruitment
Study Start Date
October 2006 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jonsson Comprehensive Cancer Center
Collaborators
National Institutes of Health (NIH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors
Keywords
recurrent pituitary tumor, ACTH-producing pituitary tumor, nonfunctioning pituitary tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1 (ACTH-secreting adenomas)
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 2 (non-secreting macroadenomas)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
rosiglitazone maleate
Intervention Description
Given orally
Primary Outcome Measure Information:
Title
Efficacy of Rosiglitazone Maleate on Cushing Disease
Description
Reduction in pituitary tumor volume by over 50% as assessed by MRI to measurements made at baseline.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony Heaney, MD
Organizational Affiliation
Jonsson Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Jonsson Comprehensive Cancer Center at UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States

12. IPD Sharing Statement

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Rosiglitazone in Treating Patients With Pituitary Tumors

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