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Temozolomide in Treating Patients With Invasive Pituitary Tumors

Primary Purpose

Brain and Central Nervous System Tumors

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
temozolomide
DNA methylation analysis
microarray analysis
protein expression analysis
proteomic profiling
laboratory biomarker analysis
Sponsored by
Jonsson Comprehensive Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring pituitary chromophobe adenoma, recurrent pituitary tumor, ACTH-producing pituitary tumor, growth hormone-producing pituitary tumor, prolactin-producing pituitary tumor, pituitary basophilic adenoma, pituitary eosinophilic adenoma, prolactin secreting adenoma, nonfunctioning pituitary tumor

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Clinically demonstrable invasive pituitary macroadenoma, including any of the following subtypes:

    • Growth hormone-secreting
    • Prolactin-secreting
    • Adrenocorticotrophic hormone-secreting
    • Non-secreting

  • Must have biochemical evidence of any of the following:

    • Acromegaly as measured by serum insulin-like growth factor-1 (IGF-1)
    • Prolactinoma as measured by serum prolactin (PRL)
    • Cushing's disease as measured by 24-hour urinary-free cortisol
  • Inadequate tumor control, defined as a visible pituitary tumor ≥ 1 cm in maximal diameter encasing the carotid arteries, and/or invading into the cavernous sinuses, and/or abutting/invading the optic chiasma as demonstrated by MRI scan with or without contrast

  • Previously assessed by radiosurgery and meets ≥ 1 of the following criteria:

    • Not a suitable candidate for radiotherapy (e.g., tumor abutting and/or invading the optic chiasm)
    • Declined radiotherapy (in light of side effects or personal choice)
    • Has not exhibited tumor shrinkage or tumor continues to grow ≥ 1 year after completion of radiotherapy

  • 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 response to arginine/growth hormone-releasing hormone testing (normal response is an increase of > 4 ng/mL)
    • Low age- and sex-matched IGF-1 levels
    • Low thyroid-stimulating hormone (TSH), 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 OR low testosterone, LH, and FSH levels in male patients
    • Serum cortisol < 3 ng/mL (at 8 am)
  • Patients diagnosed with hypopituitarism (except for post-menopausal females) are required to initiate hormone replacement therapy for the 12-month duration of the study and to discontinue hormone replacement therapy at the end of 12 months to re-evaluate hypopituitarism

PATIENT CHARACTERISTICS:

  • Able to undergo a pituitary MRI scan
  • 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 Data Safety Monitoring Board compliance officer
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for ≥ 2 months prior to, during, and for 1 month after completion of study therapy
  • No history of immunocompromise, including known HIV positivity as measured by enzyme linked immunosorbent assay (ELISA) and western blot
  • No alcohol or drug abuse within the past 6 months
  • No blood donation within the past 2 months
  • No history of noncompliance to medical regimens, potential unreliability, or inability to complete the entire study
  • No other active malignant disease within the past 5 years, except basal cell carcinoma or carcinoma in situ of the cervix
  • No active or suspected acute or chronic uncontrolled infection

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Prior pituitary surgery allowed provided the surgery failed to induce complete tumor response and the patient is deemed unsuitable for further pituitary surgeries
  • At least 3 months since prior pituitary surgery
  • More than 1 month since prior unlicensed drugs or participation in a clinical trial with an investigational drug
  • No concurrent pituitary surgery or pituitary radiotherapy
  • No other concurrent therapy to reduce pituitary tumor size

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Change from baseline of pituitary tumor control as assessed by MRI at 3, 6, 9, and 12 months
    Change in Tumor response rate (complete response or partial response) from baseline as assessed by RECIST criteria at 3, 6, 9, and 12 months
    Rebound tumor growth as assessed by MRI at 6 months after completion of treatment

    Secondary Outcome Measures

    Biochemical control as assessed by measurement of hormones secreted in excess by the pituitary tumor at baseline, at 3, 6, 9, and 12 months during treatment, and then at 2 months after completion of treatment
    Pituitary function as assessed by standard pituitary function tests at baseline and at 6 months and 12 months
    Safety and tolerability of temozolomide as assessed by NCI CTC v2.0 at screening, baseline, and then monthly until study completion
    Overall quality of life as assessed by Karnofsky performance status questionnaire periodically during study

    Full Information

    First Posted
    January 25, 2008
    Last Updated
    July 29, 2020
    Sponsor
    Jonsson Comprehensive Cancer Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00601289
    Brief Title
    Temozolomide in Treating Patients With Invasive Pituitary Tumors
    Official Title
    An Open Label, Multicenter, Phase II Study Evaluating the Safety and Efficacy of Temozolomide Treatment in Patients With Invasive Pituitary Tumors
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2012
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    funding term ended
    Study Start Date
    December 2009 (undefined)
    Primary Completion Date
    October 2010 (Actual)
    Study Completion Date
    undefined (undefined)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Jonsson Comprehensive Cancer Center

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase II trial is studying how well temozolomide works in treating patients with invasive pituitary tumors.
    Detailed Description
    OBJECTIVES: Primary To assess the effect of temozolomide on pituitary tumor growth in patients with invasive pituitary tumors. To assess the effect of temozolomide on pituitary tumor response and the duration of tumor response in these patients. Secondary To assess the effect of temozolomide on pituitary tumor hormone secretion in these patients. To assess the effect of temozolomide on other aspects of pituitary function in these patients. To assess the overall safety and tolerability of temozolomide in these patients. To assess the overall quality of life of patients treated with temozolomide. OUTLINE: This is a multicenter study. Patients receive oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of 12 courses, patients achieving a complete or partial tumor response may continue to receive temozolomide at the investigator's discretion in the absence of disease progression or unacceptable toxicity. Tumor tissue samples are collected periodically to assess methylation status of the methyl-guanine methyl-transferase promoter (MGMT) gene and to quantitate immunocytochemical expression of the tumor suppressor proteins p53, p16, and p27. Tissue samples are also analyzed by microarray and proteomics to determine a genetic "signature" of invasive vs non-invasive pituitary tumors and to determine if this signature correlates with response to temozolomide. Blood samples are also periodically for biomarker laboratory studies. Patients complete a quality of life questionnaire periodically. After completion of study therapy, patients are followed for 28 days.

    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
    pituitary chromophobe adenoma, recurrent pituitary tumor, ACTH-producing pituitary tumor, growth hormone-producing pituitary tumor, prolactin-producing pituitary tumor, pituitary basophilic adenoma, pituitary eosinophilic adenoma, prolactin secreting adenoma, nonfunctioning pituitary tumor

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    temozolomide
    Intervention Type
    Genetic
    Intervention Name(s)
    DNA methylation analysis
    Intervention Type
    Genetic
    Intervention Name(s)
    microarray analysis
    Intervention Type
    Genetic
    Intervention Name(s)
    protein expression analysis
    Intervention Type
    Genetic
    Intervention Name(s)
    proteomic profiling
    Intervention Type
    Other
    Intervention Name(s)
    laboratory biomarker analysis
    Primary Outcome Measure Information:
    Title
    Change from baseline of pituitary tumor control as assessed by MRI at 3, 6, 9, and 12 months
    Time Frame
    1 year
    Title
    Change in Tumor response rate (complete response or partial response) from baseline as assessed by RECIST criteria at 3, 6, 9, and 12 months
    Time Frame
    1 year
    Title
    Rebound tumor growth as assessed by MRI at 6 months after completion of treatment
    Time Frame
    6 months
    Secondary Outcome Measure Information:
    Title
    Biochemical control as assessed by measurement of hormones secreted in excess by the pituitary tumor at baseline, at 3, 6, 9, and 12 months during treatment, and then at 2 months after completion of treatment
    Time Frame
    14 months
    Title
    Pituitary function as assessed by standard pituitary function tests at baseline and at 6 months and 12 months
    Time Frame
    1 year
    Title
    Safety and tolerability of temozolomide as assessed by NCI CTC v2.0 at screening, baseline, and then monthly until study completion
    Time Frame
    1 year
    Title
    Overall quality of life as assessed by Karnofsky performance status questionnaire periodically during study
    Time Frame
    1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    DISEASE CHARACTERISTICS: Clinically demonstrable invasive pituitary macroadenoma, including any of the following subtypes: Growth hormone-secreting Prolactin-secreting Adrenocorticotrophic hormone-secreting Non-secreting Must have biochemical evidence of any of the following: Acromegaly as measured by serum insulin-like growth factor-1 (IGF-1) Prolactinoma as measured by serum prolactin (PRL) Cushing's disease as measured by 24-hour urinary-free cortisol Inadequate tumor control, defined as a visible pituitary tumor ≥ 1 cm in maximal diameter encasing the carotid arteries, and/or invading into the cavernous sinuses, and/or abutting/invading the optic chiasma as demonstrated by MRI scan with or without contrast Previously assessed by radiosurgery and meets ≥ 1 of the following criteria: Not a suitable candidate for radiotherapy (e.g., tumor abutting and/or invading the optic chiasm) Declined radiotherapy (in light of side effects or personal choice) Has not exhibited tumor shrinkage or tumor continues to grow ≥ 1 year after completion of radiotherapy 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 response to arginine/growth hormone-releasing hormone testing (normal response is an increase of > 4 ng/mL) Low age- and sex-matched IGF-1 levels Low thyroid-stimulating hormone (TSH), 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 OR low testosterone, LH, and FSH levels in male patients Serum cortisol < 3 ng/mL (at 8 am) Patients diagnosed with hypopituitarism (except for post-menopausal females) are required to initiate hormone replacement therapy for the 12-month duration of the study and to discontinue hormone replacement therapy at the end of 12 months to re-evaluate hypopituitarism PATIENT CHARACTERISTICS: Able to undergo a pituitary MRI scan 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 Data Safety Monitoring Board compliance officer Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for ≥ 2 months prior to, during, and for 1 month after completion of study therapy No history of immunocompromise, including known HIV positivity as measured by enzyme linked immunosorbent assay (ELISA) and western blot No alcohol or drug abuse within the past 6 months No blood donation within the past 2 months No history of noncompliance to medical regimens, potential unreliability, or inability to complete the entire study No other active malignant disease within the past 5 years, except basal cell carcinoma or carcinoma in situ of the cervix No active or suspected acute or chronic uncontrolled infection PRIOR CONCURRENT THERAPY: See Disease Characteristics Prior pituitary surgery allowed provided the surgery failed to induce complete tumor response and the patient is deemed unsuitable for further pituitary surgeries At least 3 months since prior pituitary surgery More than 1 month since prior unlicensed drugs or participation in a clinical trial with an investigational drug No concurrent pituitary surgery or pituitary radiotherapy No other concurrent therapy to reduce pituitary tumor size
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Anthony Heaney, MD
    Organizational Affiliation
    Jonsson Comprehensive Cancer Center
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Learn more about this trial

    Temozolomide in Treating Patients With Invasive Pituitary Tumors

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