To evaluate the efficacy of Lanreotide Autogel 120 mg when used as primary medical treatment in untreated de novo acromegalic patients with macroadenoma
ID
Source
Brief title
Condition
- Hypothalamus and pituitary gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the efficacy of Lanreotide Autogel 120 mg when used as primary
medical treatment in untreated de novo acromegalic patients with macroadenoma,
as assessed by evaluating the change in pituitary tumor volume at Week 48
(after 12 injection - V5) compared to baseline (V2).
A 20% reduction from the baseline volume will be considered to be clinically
significant.
Secondary outcome
1) To assess the change in tumor volume after 3 injections (V3) and 6
injections (V4) compared to baseline,
2) To assess the change in GH, IGF-1 and prolactin levels* at all assessment
time-points in comparison to the baseline visit,
3) To assess the therapeutic activity of Lanreotide Autogel 120 mg as primary
medical treatment on:
- Acromegaly symptoms,
- Quality of life (using AcroQOL),
4) To assess safety based on:
- Adverse events, clinical examination, vital signs,
- Glucose tolerance,
- Standard haematology and biochemistry,
- Gallbladder ultrasound.
* Prolactin only for patients with initial increased prolactin level (Prolactin
> 20 ng/mL).
Background summary
Recent surgical advances have contributed to improved outcomes and in
experienced hands, surgery is generally effective. However up to 10% of tumors
recur, most probably due to persistent growth of residual nonresectable tumor
tissue: for those patients with persistent GH hypersecretion and visible tumor
on MRI, reoperation by an experienced pituitary surgeon after initial surgery
by an inexperienced surgeon is recommended [7].
In one study, pituitary damage leading to transient or permanent
hypopituitarism was reported in up to 30% of patients who underwent surgery
[11], and overall rates of complications have been correlated with the number
of pituitary operations performed by the individual neurosurgeon.
Because the majority of patients with macroadenomas, especially those with
tumors extending into the cavernous sinus, will not be cured surgically,
postoperative therapy is required in most patients [7]. Thus, somatostatin
analogues were originally approved for use after noncurative pituitary surgery,
however reports of slow release formulations of somatostatin analogues, being
effective in more than 60% of patients regardless of tumor dimensions has led
to their primary use in selected patients newly diagnosed with acromegaly [10].
The primary objective of initial medical treatment is GH and IGF1 level
control. A benefit on the tumoral component of the disease is also desirable to
recommend long term medical treatment.
Previous studies demonstrated that for patients who experience significant
shrinkage, an approximately 50% decrease in pituitary mass is achieved when a
somatostatin analogue is used exclusively or before surgery or radiotherapy. In
other studies, where a definition of significant tumor shrinkage has been
provided, the results showed that 36.6% (weighted mean percentage) of patients,
receiving primary somatostatin receptor ligands therapy for acromegaly,
experienced a significant reduction in tumor size. The weighted mean percent
reduction in tumor size was 19.4% for those studies in which all patients
received somatostatin receptor ligands and showed tumor shrinkage [8, 9].
Beside their role in controlling GH and IGF1 level and elevated GH and IGF1
associated symptoms, there is a clinical indication of somatostatin
analogue-inducing tumor volume reduction. This tumor shrinkage is associated
with vital structure impingement relief, patient reassurance that the mass is
shrinking, and possibly a lowered risk of intratumoral hemorrhage.
Overall, available information on the effect of somatostatin analogues on tumor
size remains, however, limited to octreotide and needs to be demonstrated and
confirmed for Lanreotide.
Study objective
To evaluate the efficacy of Lanreotide Autogel 120 mg when used as primary
medical treatment in untreated de novo acromegalic patients with macroadenoma
Study design
Phase IIIb, multicentre, open-label, single-arm, study
Intervention
NA
Study burden and risks
Patients will not undergo more burden or risks under this protocol compared
with their normal standard care for the disease.
Taurusavenue 33B
2132 LS Hoofddorp
NL
Taurusavenue 33B
2132 LS Hoofddorp
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria:
1) The patient has given written informed consent prior to any study related procedures,
2) The patient is male or female and is aged between 18 and 75 years, inclusive,
3) Diagnosis of acromegaly defined by i) GH nadir > 1 ng/mL as assessed by an oral glucose tolerance test for non diabetic patients (central laboratory results) or a mean GH level > 1 ng/mL based on 5 samples taken every 10 to 15 minutes for diabetic patients ( central laboratory results) AND ii) IGF-1 concentrations elevated above the age- and sex-matched normal range for diabetic and non diabetic patients (central laboratory results),
4) The patient has a pituitary adenoma with a diameter * 10 mm based on Magnetic Resonance Imaging (MRI) central reading,
5) The patient has no visual field defect identified at the visual evaluation, performed by Goldman Visual Fields Analyser and Automated visual field static perimeter, except visual field abnormality at the time of screening and that is in the investigator*s opinion:
• Not related to the pituitary adenoma
• Clinically stable condition not presumed to change during the study period
• Not modifying the ability to evaluate visual field changes related to the macroadenoma.
Exclusion criteria
Exclusion criteria:
Patients will not be included in the study if:
1) The patient has a history of hypersensitivity to Lanreotide or drugs with a similar chemical structure,
2) The patient has received any unlicensed drug within the 30 days prior to the screening visit or is scheduled to receive an unlicensed drug other than Lanreotide Autogel during the course of the study,
3) The patient is likely to require treatment during the study with somatostatin analogues other than Lanreotide Autogel 120 mg, dopamine agonist, GH receptor antagonist (pegvisomant), and Cyclosporine or drugs that are not permitted by the study protocol,
4) The patient is a female at risk of pregnancy during the study and is not using acceptable contraceptive method. Females of childbearing potential must provide a negative pregnancy test at start of study and must be using oral, double barrier (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide) or injectable contraception or an intra uterine device. Non childbearing potential is defined as post-menopause for at least 1 year, surgical sterilisation or hysterectomy at least three months before the start of the study,
5) The patient is pregnant or lactating,
6) The patient has a history of, or known current, problems with alcohol abuse,
7) The patient has any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
8) The patient has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the Investigator, might jeopardise the patient*s safety or decrease the chance of obtaining satisfactory data needed to achieve the objective(s) of the study,
9) The patient has undergone pituitary surgery or pituitary radiotherapy prior to study entry,
10) The patient has previously been treated with a somatostatin analogue,
11) The patient has received a dopamine agonist or a GH receptor antagonist (pegvisomant) prior to study entry,
12) The patient is expected to require pituitary surgery (adenomectomy) or to receive radiotherapy during the study period,
13) Patients with suspected associated prolactinoma: prolactin level > 100 ng/mL (central laboratory results),
14) Patient known by Investigator, to have congenital or acquired optic nerve disease or any visual abnormality with risk of worsening during the course of the study (e.g glaucoma), influencing ability to evaluate Visual Field changes related to the macroadenoma .
Under no circumstances will patients be enrolled more than once.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-000155-34-NL |
| ClinicalTrials.gov | NCT00690898 |
| CCMO | NL20286.078.08 |