Prospective Study of Clinically Nonfunctioning Pituitary Adenomas (PAPS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by Columbia University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Pamela U. Freda, Columbia University
ClinicalTrials.gov Identifier:
NCT01556230
First received: March 9, 2012
Last updated: March 4, 2013
Last verified: March 2013
  Purpose

The purpose of this study is to carefully characterize the outcome of treatment for nonfunctioning pituitary adenomas. Pituitary adenomas are benign tumors of the pituitary gland. The study will follow 3 groups of patients with apparent pituitary adenomas (based on the MRI appearance and clinical presentation). One group of patients who will have surgery, a second who will not have surgery, and a third who have radiotherapy after surgery. The study will determine predictors of tumor growth and regrowth after surgery and if certain tumor markers can predict if the tumor will continue to grow. The study will determine whether the development of pituitary dysfunction, vision abnormalities or significant tumor growth differ between the no surgery, surgery, or radiation therapy groups. Patients in the study will also complete questionnaires on quality of life and memory function testing before and after the follow up or surgery or radiation treatment in order to determine if quality of life or memory are affected by these treatments.


Condition
Pituitary Adenoma
Pituitary Tumor

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Study of Clinically Nonfunctioning Pituitary Adenomas

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Pituitary tumor enlargement [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Number of patients with tumor enlargement over the study period

  • Development of hypopituitarism [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Number of patients with the development of hypopituitarism over the time frame.


Secondary Outcome Measures:
  • Neurocognitive function change [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Change in neurcognitive function test score over the time frame of the study.


Estimated Enrollment: 350
Study Start Date: March 2009
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
Non-Surgery
Patients with clinically nonfunctioning pituitary adenomas may be treated with surgery or by observation alone depending on the tumor size and other factors. The decision whether or not to treat the tumor with surgery was made by the patient and their physicians. The purpose of this study is to carefully characterize the outcome of this conservative nonsurgical treatment including whether or not the tumor grows, if there is any change in hormone levels and whether surgery becomes necessary in the future.
Surgery
Patients with clinically nonfunctioning pituitary adenomas may be treated with surgery or by observation alone depending on the tumor size and other factors. The decision whether or not to treat the tumor with surgery is made by the patient and their physician. Patient who have decided to have surgery are invited to participate in this study that will evaluate the outcome of prospective follow up for you before and after surgery. The purpose of this study is to carefully characterize the outcome of surgical treatment including whether or not the tumor regrows, if the patient any change in hormone levels, and whether radiotherapy is needed in the future.
Radiotherapy (Radiation)
Patients with clinically nonfunctioning pituitary adenomas may be treated initially with surgery or by observation alone depending on the tumor size and other factors. Some patients receive radiotherapy at some time after the surgery was done, typically because the tumor could not be fully removed and/or has regrown. The decision whether or not to treat the tumor with radiotherapy was made by the patient and their physicians. As the patient has decided to have radiotherapy for their pituitary tumor they are being invited to participate in this study that will evaluate the outcome of prospective follow up for you before and after radiotherapy. The purpose of this study is to carefully characterize the outcome of radiotherapy treatment including whether or not the tumor regrows or if there is a change in hormone levels.

  Hide Detailed Description

Detailed Description:

Research question(s):

This study conducts a comprehensive prospective study of clinically nonfunctioning pituitary adenomas. The study aims to test the hypothesis that conservative, nonsurgical management of clinically nonfunctioning pituitary lesions that do not meet criteria for surgery as initial therapy is safe with respect to changes in pituitary function, tumor size and visual and neurological function. The study also aims to determine the outcome of transsphenoidal surgery and also in some cases the addition of pituitary radiotherapy for symptomatic, clinically nonfunctioning pituitary tumors and test the hypothesis that radiotherapy will reduce the recurrence rate of pituitary tumors. In addition, the study will consider whether clinical features or immunohistochemical markers of tumor proliferation predict tumor regrowth. In particular the study will test the hypothesis that the silent corticotroph tumor subtype, characterized by elevated plasma levels of ACTH or its precursor, POMC, is associated with an increased tumor recurrence rate. The study also aims to determine for the first time, prospectively, the impact of conservative follow up, surgery and RT on quality of life and neurocognitive function in patients with clinically nonfunctioning pituitary lesions.

Study Purpose:

This project is the first comprehensive prospective study of clinically nonfunctioning pituitary adenomas (CNFAs). The purpose of the project is to answer a number of important questions about the evaluation and management of these lesions. No rigorously developed guidelines exist for the evaluation, therapy or longterm monitoring of CNFAs. Rather, current management strategies are loosely defined and based almost exclusively on data from retrospectively reported series. As a result, a number of significant gaps exist in our current knowledge about CNFA management. With regard to asymptomatic pituitary lesions, the appropriate initial evaluation and followup strategies, as well as the safety of conservative, nonsurgical management are unknown. For symptomatic tumors, surgery is the initial treatment of choice, but many tumors recur and there exists no means of reliably predicting those at risk for recurrence. Further study of predictors of aggressive, recurrent tumors is needed. One possible predictor requiring study is the "silent" corticotroph tumor type. The safety of conservative followup for patients with small tumor remnants after surgery is not known. The need for radiation for all such patients remains unclear since the risks vs. benefits of postoperative RT for residual/recurrent tumors have not been prospectively studied. The longterm management of CNFA should also consider the impact of therapy on quality of life and neurocognitive function, but these have never been evaluated longitudinally. Our large prospective study is needed to answer these important questions about CNFA management.

Study Design PROTOCOL I: Prospective Study of the outcome of conservative nonsurgical management of patients with asymptomatic, clinically nonfunctioning pituitary lesions. This protocol will evaluate prospectively the outcome of nonsurgical management of clinically nonfunctioning pituitary lesions that do not appear to need surgery as their initial therapy. The overall design consists of an initial baseline evaluation and then serial prospective follow up studies over time for up to 5 years of follow up. The study will evaluate laboratory testing, clinical examinations, quality of life and neurocognitive function in these patients. We will also collect data on visual fields and MRI studies of the pituitary tumor that are done prospectively as part of clinical care to evaluate these patients. Data to be collected will include the prevalence of pituitary dysfunction at presentation, the safety of conservative nonsurgical management of patients with asymptomatic, clinically nonfunctioning pituitary lesions with respect to the development of symptomatic tumor enlargement and pituitary dysfunction, the prevalence of the silent corticotroph tumor type that is characterized by elevated plasma levels of ACTH or its precursor, POMC, and if it is associated with an increased tumor recurrence rate and prospectively assess quality of life and neurocognitive function in patients with clinically nonfunctioning pituitary lesions treated without surgery.

PROTOCOL II : Prospective study of the outcome of patients with symptomatic, clinically nonfunctioning pituitary tumors who are treated with transsphenoidal surgery and in some cases also radiotherapy. This protocol will evaluate prospectively the outcome of surgical management of asymptomatic clinically nonfunctioning pituitary lesions. The overall design consists of an initial baseline evaluation and then serial prospective follow up studies over time with up to 5 years of follow up. The study will evaluate laboratory testing, clinical examinations, quality of life and neurocognitive function in these patients. We will also collect data on visual fields and MRI studies of the pituitary tumor that are done prospectively as part of clinical care to evaluate these patients. Data to be collected will be analyzed to determine the safety of observation alone following surgery for patients who do not have a clinically significant tumor remnant, if the silent corticotroph tumor type is characterized by elevated plasma levels of ACTH or its precursor, POMC, and if it is associated with an increased tumor recurrence rate. A group of patients who are planning RT will also be studied by these same procedures before and after RT in order to determine if the outcomes of patients who receive RT for treatment of tumor regrowth to that of those who do not receive RT with respect to further tumor growth, endocrine or neurological dysfunction. We will also prospectively assess quality of life and neurocognitive function in patients with clinically nonfunctioning pituitary lesions treated with surgery alone or those who also receive radiotherapy.

Study Subjects:

Group I: A group of 100 adult patients with pituitary lesions that do not require surgical intervention will be studied as part of Protocol I. Eligible patients will have a pituitary lesion demonstrated on MRI to be consistent with an adenoma (not a cystic lesion such as a Rathke's cleft cyst). Patients meeting any of the following indications for surgery will be excluded: presence of visual or neurological deficits due to the tumor, tumor impingement on the optic chiasm and physical or laboratory abnormalities consistent with a biologically active hormone secreting tumor. Some patients may have elevations of pituitary hormones such as ACTH, but no elevation of end organ hormone such as cortisol. Patients with a pituitary tumor that makes a functioning hormone and has a resultant biochemical and/or clinical syndrome associated with it would be treated as appropriate with surgery or medication and would not be followed conservatively without surgery.

Group II: A second group of 250 adult patients with pituitary lesions that require surgical intervention and who are planning on surgery will be studied as part of Protocol II. Although we have established general guidelines for who should be recommended for surgery, the formal decision whether or not to undergo surgery is a medical one made by the patient and the Neurosurgeon.

Group III: Patients who are undergoing Radiotherapy and previously underwent surgery for their pituitary tumor are also eligible to participate.

Subject Recruitment:

Patients in both study groups will be recruited directly from the office of the participating Neurosurgeon, Dr. Jeffrey Bruce and by referral to our Neuroendocrine Unit from the other participating Neurosurgeon, Dr. Kalmon Post.

Patients may also be recruited from out Neuroendocrine clinical practice or referred by outside physicians for participation in the study. Each patient will first be approached about participation in the study by their physician. It they are interested then the study team will discuss the study further with them.

Study Procedures:

Protocol I:

Baseline Visit: History and physical examination, laboratory testing: prolactin, ACTH, cortisol, free thyroxine, TSH, LH, FSH, testosterone (men), GH, IGFI, POMC, asubunit, 24hour for urine free cortisol.

Follow up visits: 6 and 12 months and yearly after the baseline visit. Testing at each visit includes an update of the history, laboratory testing as done at the baseline visit, physical examinations and completion of quality of life and neurocognitive testing, visual field testing and pituitary MRI scans. Those patients who develop a clinically significant enlargement of the tumor that meets a surgical indication will be given the option of entering Protocol II. Tumor enlargement will be considered clinically significant if the tumor grows to impinge on the optic chiasm or causes any visual disturbance or other neurological abnormality.

Quality of life testing: Patients will be administered general health questionnaires SF36, NHP (Nottingham health profile) and disease specific questionnaires QLSH (quality of life satisfaction hypopituitarism) and QoL AGHD (Quality of life assessment of GH deficiency in adults). Neurocognitive testing: Patients will be administered a series of standard and widely used tests of neurocognitive function, primarily measures of memory and neurocognitive function, by trained personnel.

Protocol II Baseline Visit: History and physical examination, laboratory testing (as in Protocol I), visual fields, quality of life, neurocognitive testing (as in Protocol I) and MRI scan. Follow up visits after surgery: 6 and 12 months and yearly after the baseline visit include the testing as done at the baseline visit. Surgical procedures will take place as per routine clinical practice of the surgeon. Records from the surgical procedure including extent and invasion of the tumor and occurrence of endocrine abnormalities postoperatively such as diabetes insipidus or new hypopituitarism will be recorded. If patients are referred for radiotherapy if they have residual tumor or regrowth of their tumor then they will be followed also prospectively with a baseline visit and follow up visits after radiotherapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Any persons diagnosed with a non-functioning pituitary adenoma that is willing to travel to our study center at Columbia University in New York, NY for all study visits.

Criteria

Inclusion Criteria:

  • Diagnosed with a pituitary tumor that does not secrete hormones AND
  • Men and women 18 years of age or older AND
  • Patient and their doctor have decided that the patient will have radiotherapy OR
  • Patient and their doctor have decided that the patient will have surgery OR
  • Patient and their doctor have decided that that the patient will have surgery
  • Pituitary lesion is greater than or equal to 7.0 mm in maximal diameter
  • Prolactin level is less than 100 ng/ml
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01556230

Contacts
Contact: Amanda N Wade, MPH 212-305-7243 anw2124@columbia.edu
Contact: Jean Carlos Fernandez, MD 212-305-4921 sjf2132@columbia.edu

Locations
United States, New York
Columbia University College of Physicians & Surgeons Recruiting
New York, New York, United States, 10032
Contact: Amanda N. Wade, MPH    212-305-7243    anw2124@columbia.edu   
Contact: Jean Carlos Fernandez, MD    212-305-4921    sjf2132@columbia.edu   
Principal Investigator: Pamela U. Freda, MD         
Sub-Investigator: Sharon L Wardlaw, MD         
Sub-Investigator: Jeffrey N Bruce, MD         
Sub-Investigator: Steven R Isaacson, MD         
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Pamela U. Freda, MD Columbia University College of Physicians&Surgeons
  More Information

No publications provided

Responsible Party: Pamela U. Freda, Associate Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT01556230     History of Changes
Other Study ID Numbers: AAAE1260, R01NS070600
Study First Received: March 9, 2012
Last Updated: March 4, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Columbia University:
pituitary gland
pituitary adenoma
pituitary tumor
hypophysis
endocrine
neuroendocrine
hormone

Additional relevant MeSH terms:
Adenoma
Pituitary Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Hypothalamic Neoplasms
Supratentorial Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Hypothalamic Diseases
Pituitary Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 30, 2014