Temozolomide in Treating Patients With Invasive Pituitary Tumors - Full Text View

Sponsor:	Jonsson Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00601289

Purpose

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	Intervention	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 II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	An Open Label, Multicenter, Phase II Study Evaluating the Safety and Efficacy of Temozolomide Treatment in Patients With Invasive Pituitary Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pituitary Tumors

Drug Information available for: Temozolomide

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pituitary tumor control as assessed by MRI at baseline and at 3, 6, 9, and 12 months [ Designated as safety issue: No ]
Tumor response rate (complete response or partial response) as assessed by RECIST criteria at baseline and at 3, 6, 9, and 12 months [ Designated as safety issue: No ]
Duration of tumor response as assessed by RECIST criteria at baseline and at 3, 6, 9, and 12 months [ Designated as safety issue: No ]
Rebound tumor growth as assessed by MRI at 6 months after completion of treatment [ Designated as safety issue: No ]

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 [ Designated as safety issue: No ]
Pituitary function as assessed by standard pituitary function tests at baseline and at 6 months and 12 months [ Designated as safety issue: No ]
Safety and tolerability of temozolomide as assessed by NCI CTC v2.0 at screening, baseline, and then monthly until study completion [ Designated as safety issue: Yes ]
Overall quality of life as assessed by Karnofsky performance status questionnaire periodically during study [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	January 2008
Estimated Primary Completion Date:	December 2011 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 triodothyronine (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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601289

Locations

United States, California
Jonsson Comprehensive Cancer Center at UCLA	Recruiting
Los Angeles, California, United States, 90095-1781
Contact: Clinical Trials Office - Jonsson Comprehensive Cancer Center a 888-798-0719

Sponsors and Collaborators

Jonsson Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Anthony Heaney, MD

Jonsson Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000577534, UCLA-06-12-080, SPRI-UCLA-06-12-080, 07-05-077-01
Study First Received:	January 25, 2008
Last Updated:	July 7, 2009
ClinicalTrials.gov Identifier:	NCT00601289 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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:

Pituitary Neoplasms
Pituitary Diseases
Hypothalamic Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Nervous System Diseases
Endocrine System Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Brain Diseases
Temozolomide

Supratentorial Neoplasms
Pharmacologic Actions
Brain Neoplasms
Neoplasms
Neoplasms by Site
Therapeutic Uses
Hypothalamic Neoplasms
Antineoplastic Agents, Alkylating
Alkylating Agents
Nervous System Neoplasms
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010