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Prospective Study of Clinically Nonfunctioning Pituitary Adenomas


N/A
18 Years
N/A
Open (Enrolling)
Both
Pituitary Adenoma, Pituitary Tumor

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Trial Information

Prospective Study of Clinically Nonfunctioning Pituitary Adenomas


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.


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

Type of Study:

Observational

Study Design:

Observational Model: Cohort, Time Perspective: Prospective

Outcome Measure:

Pituitary tumor enlargement

Outcome Description:

Number of patients with tumor enlargement over the study period

Outcome Time Frame:

5 years

Safety Issue:

No

Principal Investigator

Pamela U. Freda, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Columbia University College of Physicians&Surgeons

Authority:

United States: Institutional Review Board

Study ID:

AAAE1260

NCT ID:

NCT01556230

Start Date:

March 2009

Completion Date:

Related Keywords:

  • Pituitary Adenoma
  • Pituitary Tumor
  • pituitary gland
  • pituitary adenoma
  • pituitary tumor
  • hypophysis
  • endocrine
  • neuroendocrine
  • hormone
  • Adenoma
  • Pituitary Neoplasms

Name

Location

Columbia University College of Physicians & SurgeonsNew York, New York  10032