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Use of Somatostatin Analogue Therapy as Primary Medical Treatment of Acromegaly

Phase 3
18 Years
Not Enrolling

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Trial Information

Use of Somatostatin Analogue Therapy as Primary Medical Treatment of Acromegaly

Acromegaly is a disorder caused by excessive secretion of growth hormone (GH) usually
associated with a GH-secreting pituitary adenoma composed of somatotrophs or
somatomammotrophs. Acromegaly can also rarely (less than 1% of cases) be caused by
somatotroph hyperplasia, caused by the overproduction of Growth Hormone Releasing Hormone
(GHRH). The condition is rare with an estimated incidence of 200 new cases per year in the
UK based on a population of 50 million.

At the current time, the primary treatment of patients presenting with acromegaly due to a
functional pituitary tumour is surgery (transsphenoidal adenectomy). The aim of surgery is
to cure the condition i.e. return GH levels to normal. The advantage of this treatment
modality for individuals with small tumours is the likelihood of cure with a low probability
of long term defects in other hormonal axes. With larger tumours, however, the chance of
cure is less good, as is the chance of preserving other hormonal axes post-operatively.

The clinical studies that have been performed to date leave one key question unanswered:
would treatment with somatostatin analogue therapy pre-operatively, reduce tumour size
enough to produce a clinically significant improvement in surgical results with the
particular emphasis on lateral extension of tumour. Specifically, would surgical
pre-treatment increase the surgical cure rate? Would surgical pre-treatment with a
somatostatin analogue reduce the need for radiotherapy or the subsequent incidence of other
hormonal axes defects? This study aims to answer these questions.

Patients will be treated for 12 months with Somatuline Autogel which is administered by deep
sub-cutaneous injection. Somatuline Autogel will be the somatostatin analogue used for this
study. It is already routinely used for the treatment of Acromegaly in this region. As the
primary aim of the study is tumour shrinkage and there is some evidence that greater tumour
shrinkage is achieved with higher doses then the maximum tolerated dose will be used.
Injections will be performed every 28 days. The first dose administered will be 60 mg, if
this is tolerated 90 mg will be used for the second injection and again, if the dose is
tolerated then 120 mg will be given for the third and all subsequent injections.

Primary Objective: To test the hypothesis that a twelve month period of primary medical
treatment of acromegaly with Somatuline Autogel will produce clinically significant
reductions in tumour size from Baseline to Month 12 as assessed using MRI.

Secondary Objectives: Within-patient Comparisons of the effect of Primary Treatment with
Somatuline Autogel.

- To assess the change in tumour size at Month 3 and Month 6 compared to baseline
assessed using MRI.

- To assess the change in the GH and IGF-1 levels at all assessment timepoints in
comparison to the baseline visit.

- To assess the change in visual fields at all assessment timepoints in comparison to
baseline, as assessed using a Goldman Visual Fields Analyser.

- To assess the change in patient symptom scores at all assessment timepoints in
comparison to the baseline visit as assessed using numerical rating scales.

- To assess the change in quality of life scores (as assessed using the SF-36
questionnaire) at all assessment timepoints in comparison to the baseline visit.

- To determine the incidence of occurrence of new hormonal axes defects arising
pre-operatively between baseline and Month 12.

- To determine the proportion of patients requiring surgery during the twelve month study
period (i.e. those with tumour progression or intolerable symptoms on medical therapy).

- To evaluation the safety and tolerability of each dose of Somatuline Autogel, as
assessed by:

- the maximum tolerated dose for each patient,

- the incidence of adverse events (including findings on liver and gallbladder

- changes in concomitant medication,

- the incidence of clinically significant changes in vital signs or ECG,

- the incidence of clinically significant laboratory or physical examination

Inclusion Criteria:

Patients must satisfy all of the following entry criteria before they will be allowed to
participate in the study:

- The patient must give written (personally signed and dated) informed consent before
completing any study-related procedure, which means any assessment or evaluation that
would not have formed part of their normal medical care.

- The patient is over 18 years of age inclusive.

- The patient has active acromegaly as diagnosed by oral glucose tolerance test and
IGF-1 measurement. Acromegaly must be confirmed prior to study entry based on
failure to suppress GH during an oral glucose tolerance test and IGF-1 above the
normal range.

- The patient has a pituitary adenoma tumour size greater than 5 mm along the longest
axis on MRI.

- The patient has a life expectancy of at least 2 years.

- The patient is able and willing to comply with the requirements of the protocol.

Exclusion Criteria:

- The patient is considered unfit for surgery due to comorbidity that is unlikely to
resolve with control of acromegaly.

- The patient has a significant visual field defect thought to be due to optic chiasm
compression at the time of presentation where the risk of visual loss is considered
too great to delay surgery. (Note: Not all patients with visual field defects will
be excluded - this decision will be made at the joint pituitary clinic). Following
informed discussion with the individual medical therapy will be offered with close
monitoring of visual fields as per protocol. If visual field assessment shows a
further deterioration then surgery will be offered at that point. The available
literature strongly supports the view that further tumour growth is unlikely during
somatostatin analogue therapy.

- The patient has a pituitary adenoma tumour of 5 mm or less along the longest axis,
with margins clearly defined within pituitary fossa.

- The patient has had any prior pituitary surgery (adenectomy).

- The patient has received pituitary radiotherapy within one year prior to screening.

- The patient has been previously treated with a GH antagonist or a somatostatin

- The patient has clinically significant renal or hepatic abnormalities.

- The patient has a known allergy or hypersensitivity to any of the test compounds or

- The patient is pregnant or lactating (female patients of child-bearing potential
(i.e. who are not surgically sterile or at least 1 year post-last menstrual period)
must have a negative urine pregnancy test at the baseline visit).

- The patient is a female at risk of pregnancy during the study, not taking adequate
precautions against pregnancy.

- The patient has received any investigational drug therapy within 30 days prior to the
study, or is scheduled to receive such a drug during the study period.

- The patient has previously entered this study.

Type of Study:


Study Design:

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

Outcome Measure:

Reductions in tumour size from Baseline to Month 12 as assessed using MRI.

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

Daniel E Flanagan, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Plymouth Hospitals NHS Trust


United Kingdom: National Health Service

Study ID:

Sponsor Protocol no. AcMed 01



Start Date:

November 2005

Completion Date:

June 2010

Related Keywords:

  • Acromegaly
  • Acromegaly
  • Acromegaly