Know Cancer

forgot password

An Open Label, Multicenter, Phase II Study Evaluating the Safety and Efficacy of Temozolomide Treatment in Patients With Invasive Pituitary Tumors

Phase 2
18 Years
75 Years
Not Enrolling
Brain and Central Nervous System Tumors

Thank you

Trial Information

An Open Label, Multicenter, Phase II Study Evaluating the Safety and Efficacy of Temozolomide Treatment in Patients With Invasive Pituitary Tumors



- 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

- To assess the effect of temozolomide on other aspects of pituitary function in these

- 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.

Inclusion Criteria


- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Change from baseline of pituitary tumor control as assessed by MRI at 3, 6, 9, and 12 months

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Anthony Heaney, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Jonsson Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2009

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • 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
  • Nervous System Neoplasms
  • Pituitary Neoplasms
  • Central Nervous System Neoplasms