Nervous System Diseases

Gland and Hormone Related Diseases

All Conditions

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Pituitary Diseases

Acromegaly

Pituitary Neoplasms

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Bone Diseases

Bone Diseases, Endocrine

Endocrine Gland Neoplasms

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

All Drugs and Chemicals

Bone Density Conservation Agents

Calcium

Calcium, Dietary

Group 1 - Acromegaly patients, Group 2 - Nonfunctioning pituitary adenoma patients (control)

Adriana Ioachimescu, MD, PhD

The purpose of the study is to evaluate the Calcium homeostasis in adult patients with uncontrolled acromegaly. The measurements will be repeated 3-6 months after the treatment of acromegaly (surgical or medical). The control group consists of patients with nonfunctioning pituitary tumors who will undergo surgical removal.

Calcitriol is the active form of vitamin D. Parathyroid hormone (PTH) is secreted by the parathyroid glands in the neck. Both these chemicals are responsible for keeping the levels of calcium and phosphorous normal and also play a role in bone health. They can be measured in the blood. In some disorders, PTH or calcitriol levels are elevated, which results in increased calcium absorption from the gut, increased calcium in the bloodstream, and increased calcium excretion in the urine. Increased calcium in the urine can lead to the development of kidney stones. Increased calcium in the bloodstream can have adverse effects on the heart, gut, kidneys, and bones.

Acromegaly is a condition where a pituitary tumor secretes excessive amounts of growth hormone. Patients with acromegaly have been found to have a higher prevalence of kidney stones, urinary calcium, and serum calcium when compared to normal adults. The reason for this is unknown but a suggested mechanism is that growth hormone stimulates the production of calcitriol or PTH. If this is true, then treatment of acromegaly resulting in lower growth hormone levels should also result in lower blood and urine calcium levels. The investigators want to see if patients with acromegaly have high calcitriol, and vitamin D binding protein, or PTH levels and see if they change after treatment of the condition. The investigators also want to assess the amount of calcium in the urine, before and after treatment.

Patients with acromegaly may have disorders of bone health. The reason for this is unknown but a suggested mechanism is that growth hormone affects bone remodeling. The investigators want to see if patients with acromegaly have abnormal bone markers, specifically PINP, CTX, and TRAP, and to see if they change after treatment of the condition.

In order to see if the results are specific to patients with acromegaly, the investigators also want to check these levels in patients who do not have acromegaly, but have a "nonfunctioning" pituitary tumor. A nonfunctioning pituitary tumor is one that does not secrete excessive hormones in the bloodstream.

The specific aims of this study are:

1. To describe baseline calcitriol/PTH status in patients with uncontrolled acromegaly.
2. To assess the change in calcitriol/PTH levels after treatment with acromegaly (surgical or medical).
3. To evaluate the calcium and calcitriol/PTH levels in patients with acromegaly compared to patients with nonfunctioning pituitary adenomas.

This is a voluntary study. Adult patients with a diagnosis of acromegaly or a clinically nonfunctioning pituitary tumor receiving treatment at the Emory University Pituitary center will be given the opportunity to enroll in the study. Those that agree to participate will need to give written informed consent. Approximately 3 tablespoons (44ml) of blood will be drawn at enrollment for testing of vitamin D status and parathyroid hormone. If patients are already undergoing a blood draw for standard laboratory tests, then the volume of 44ml of blood will be obtained at the same time in order to avoid an additional needle stick. In addition, a 24-hour urine collection will be obtained to assess the amount of calcium present in the urine. Please note that medical or surgical therapy for your pituitary condition is determined by your endocrinologist and/or neurosurgeon and not part of the research study.

Within 6 months after treatment for pituitary treatment is initiated, when patients return to Emory University pituitary clinic for routine visit, laboratory data (vitamin D and parathyroid hormone) and repeat urine studies (24 hour urine collection) will be collected.

The confidentiality will be respected in all encounters. No personal identifiers are disclosed in any publications. Hard copy data will be kept securely in a locked office building with limited access and electronic data will always be password protected with access available to study personnel only. If abnormal results are discovered as part of testing done for this study, those results will be released to the patient's primary physician. All patients will be undergoing standard therapy for their pituitary disorder.

Results of this study may have important implications for future studies that are designed to evaluate the mechanism of how growth hormone may increase calcitriol levels.

Blood and urine samples obtained from subjects.

Calcium Homeostasis in Acromegaly: Effect of Surgical/Medical Treatment and Comparison With Nonfunctioning Pituitary Tumors

Calcium Homeostasis in Acromegaly: Effect of Surgical/Medical Treatment and Comparison With Nonfunctioning Pituitary Tumors.

To describe baseline calcitriol/PTH status in patients with uncontrolled acromegaly, with subanalyses based on presence of hyperprolactinemia.

To assess the change in calcitriol/PTH levels after treatment with acromegaly, with subanalyses based on type of therapy (surgical or medical).

To evaluate the calcium and calcitriol/PTH levels in patients with acromegaly compared to patients with nonfunctioning pituitary adenomas, with subanalyses based on presence of hyperprolactinemia in either group.

Emory University

Associate Professor

Symptoms and General Pathology

Adenoma

Recurrence

Prolactinoma

Adenoma, Basophil

Adenoma, Chromophobe

Adenoma, Acidophil

Antineoplastic Agents

Hormones

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

temozolomide

DNA methylation analysis

microarray analysis

protein expression analysis

proteomic profiling

laboratory biomarker analysis

Anthony Heaney, MD

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.

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.

Temozolomide in Treating Patients With Invasive Pituitary Tumors

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

Jonsson Comprehensive Cancer Center

Glioma

Glioblastoma

Astrocytoma

Meningioma

Oligodendroglioma

Neoplasm Metastasis

Medulloblastoma

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Pinealoma

Ependymoma

Craniopharyngioma

Adamantinoma

Gliosarcoma

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Solitary Fibrous Tumors

Hemangiopericytoma

Choroid Plexus Neoplasms

Glioma, Subependymal

Germ Cells Tumors

Acute Graft Versus Host Disease

Brain Tumor, Adult

Pineocytoma

Anaplastic Astrocytoma

Anaplastic Oligodendroglioma

Neuroepithelioma

Diffuse Astrocytoma

Supratentorial Primitive Neuroectodermal Tumor

Pineoblastoma

Pilocytic Astrocytoma

Anaplastic Ependymoma

Embryonal Tumor With Multilayered Rosettes

Subependymoma

Myxopapillary Ependymoma

Patients complete questionnaires about the side effects they experience from radiosurgery. The questionnaires are completed at baseline and at 1 week, 1 month, and 2 months after radiosurgery.

Questionnaire

John Suh, MD

RATIONALE: Learning about the side effects of stereotactic radiosurgery in patients with brain tumors or other brain disorders may help doctors plan treatment and help patients live more comfortably.

PURPOSE: This clinical trial is studying the acute side effects in patients who are undergoing stereotactic radiosurgery for brain tumors or other brain disorders.

OBJECTIVES:

* Determine the incidence and types of acute complications in patients undergoing stereotactic radiosurgery for brain tumors or other brain disorders.
* Determine the time frame for development and resolution of these complications in these patients.
* Determine the severity of these complications in these patients.

OUTLINE: Patients undergo stereotactic radiosurgery. Patients also complete questionnaires about the side effects they experience from radiosurgery. The questionnaires are completed at baseline and at 1 week, 1 month, and 2 months after radiosurgery.

PROJECTED ACCRUAL: A total of 94 patients will be accrued for this study.

Determine the incidence and types of acute complications in patients undergoing stereotactic radiosurgery for brain tumors or other brain disorders.

Acute Side Effects in Patients Who Are Undergoing Stereotactic Radiosurgery for Brain Tumors or Other Brain Disorders

Prospective Study on the Short-Term Adverse Effects From Gamma Knife Radiosurgery

Patients undergo stereotactic radiosurgery. Patients also complete questionnaires about the side effects they experience from radiosurgery. The questionnaires are completed at baseline and at 1 week, 1 month, and 2 months after radiosurgery.

Case Comprehensive Cancer Center

Hypoglycemic Agents

Maleic acid

Rosiglitazone

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.

rosiglitazone maleate

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.

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.

Rosiglitazone in Treating Patients With Pituitary Tumors

Rosiglitazone (Peroxisome Proliferating Activating Receptor-gamma {PPAR-y} Ligand) Treatment of Pituitary Tumors

Reduction in pituitary tumor volume by over 50% as assessed by MRI to measurements made at baseline.

National Institutes of Health (NIH)

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.

rosiglitazone maleate : Given orally

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 12 months in the absence of disease progression or unacceptable toxicity.

rosiglitazone maleate : Given orally

Group 2 (Non-secreting Macroadenomas)

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Recruitment was the main limitation. Patients were available but were not interested in the study due to possible side effects of the study drug.

Anthony Heaney, M.D. Ph.D

No data was analyzed for this outcome measure as there was insufficient data to perform analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Calcium Homeostasis in Acromegaly: Effect of Surgical/Medical Treatment and Comparison With Nonfunctioning Pituitary Tumors	NCT01568359	Acromegaly Nonfunctioning ...		18 Years -	Emory University
Temozolomide in Treating Patients With Invasive Pituitary Tumors	NCT00601289	Brain and Centr...	temozolomide DNA methylation... microarray anal... protein express... proteomic profi... laboratory biom...	18 Years - 75 Years	Jonsson Comprehensive Cancer Center
Acute Side Effects in Patients Who Are Undergoing Stereotactic Radiosurgery for Brain Tumors or Other Brain Disorders	NCT00255671	Brain and Centr... Metastatic Canc... Radiation Toxic...	Questionnaire	18 Years -	Case Comprehensive Cancer Center
Rosiglitazone in Treating Patients With Pituitary Tumors	NCT00616642	Brain and Centr...	rosiglitazone m...	18 Years - 65 Years	Jonsson Comprehensive Cancer Center
Yttrium Y 90 SMT 487 in Treating Patients With Refractory or Recurrent Cancer	NCT00006368	Brain and Centr... Breast Cancer Gastrointestina... Islet Cell Tumo... Lung Cancer Lymphoma Melanoma (Skin) Neoplastic Synd...	yttrium Y 90-ed...	18 Years -	Novartis
Temozolomide in Treating Patients With Invasive Pituitary Tumors	NCT00601289	Brain and Centr...	temozolomide DNA methylation... microarray anal... protein express... proteomic profi... laboratory biom...	18 Years - 75 Years	Jonsson Comprehensive Cancer Center
Rosiglitazone in Treating Patients With Pituitary Tumors	NCT00616642	Brain and Centr...	rosiglitazone m...	18 Years - 65 Years	Jonsson Comprehensive Cancer Center

Spots Global Cancer Trial Database for nonfunctioning pituitary tumor