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Temozolomide in Treating Patients With Invasive Pituitary Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00601289
Recruitment Status : Withdrawn (funding term ended)
First Posted : January 28, 2008
Last Update Posted : July 31, 2012
National Cancer Institute (NCI)
Information provided by:
Jonsson Comprehensive Cancer Center

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.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: temozolomide Genetic: DNA methylation analysis Genetic: microarray analysis Genetic: protein expression analysis Genetic: proteomic profiling Other: laboratory biomarker analysis Phase 2

Detailed Description:



  • 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.


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label, Multicenter, Phase II Study Evaluating the Safety and Efficacy of Temozolomide Treatment in Patients With Invasive Pituitary Tumors
Study Start Date : December 2009
Actual Primary Completion Date : October 2010

Primary Outcome Measures :
  1. Change from baseline of pituitary tumor control as assessed by MRI at 3, 6, 9, and 12 months [ Time Frame: 1 year ]
  2. 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 ]
  3. Rebound tumor growth as assessed by MRI at 6 months after completion of treatment [ Time Frame: 6 months ]

Secondary Outcome Measures :
  1. 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 ]
  2. Pituitary function as assessed by standard pituitary function tests at baseline and at 6 months and 12 months [ Time Frame: 1 year ]
  3. 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 ]
  4. Overall quality of life as assessed by Karnofsky performance status questionnaire periodically during study [ Time Frame: 1 year ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00601289

Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
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Study Chair: Anthony Heaney, MD Jonsson Comprehensive Cancer Center

Layout table for additonal information Identifier: NCT00601289     History of Changes
Other Study ID Numbers: CDR0000577534
P30CA016042 ( U.S. NIH Grant/Contract )
First Posted: January 28, 2008    Key Record Dates
Last Update Posted: July 31, 2012
Last Verified: July 2012

Keywords provided by Jonsson Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
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Pituitary Diseases
Nervous System Neoplasms
Central Nervous System Neoplasms
Pituitary Neoplasms
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Neoplasms by Site
Endocrine Gland Neoplasms
Hypothalamic Neoplasms
Supratentorial Neoplasms
Brain Neoplasms
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents