AcromegalyNCT00616408
Prediction of Tumor Shrinkage in Acromegaly
An observational study of Acromegaly, run by Federico II University at 1 site in Italy.
Trial summary
In the last two decades, somatostatin analogs have become a cornerstone of medical therapy for acromegaly. One year of treatment with octreotide-LAR (LAR) controls GH and IGF-I excess in 54% and 63% of unselected patients, with an increasing proportion of subjects achieving IGF-I normalization prolonging the… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Acromegaly
- What is being tested?
- Octreotide-LAR
- How many people
- 61 participants
- Where
- 1 siteItaly
- Study dates
- Jan 1997to Dec 2007
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Newly diagnosed patients with acromegaly treated first-line with octreotide-LAR
Who may be able to join
- No previous treatment for acromegaly
Who cannot join
- primary surgery
- concomitant hyperprolactinemia requiring combined somatostatin analogues and dopamine-agonist treatment
- primary treatment with lanreotide
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples
Naples, 80131
About this study
Official title: Predictive Value of 3 Months Results on 12 Months Tumor Shrinkage After First-Line Octreotide-LAR Therapy in Patients With Acromegaly
In the last two decades, somatostatin analogs have become a cornerstone of medical therapy for acromegaly. One year of treatment with octreotide-LAR (LAR) controls GH and IGF-I excess in 54% and 63% of unselected patients, with an increasing proportion of subjects achieving IGF-I normalization prolonging the treatment. Clinically significant tumor shrinkage (20-30% vs. baseline) has also been reported, with a higher proportion in patients treated first-line [231 of 448 patients (52%)] than in those treated after surgery and/or radiotherapy [52 of 248 patients (21%)]. The highest rate of clinically significant shrinkage (>20%) occurred in patients treated first-line with LAR (80%) as compared to the short-lasting octreotide formulation (50%) or lanreotide slow-release formulation (35%. In 99 de novo patients with acromegaly, we recently reported control of GH levels in 57.6%, of IGF-I levels in 45.5% and a greater than 50% tumor shrinkage in 44.4% after 12 months of first-line treatment with somatostatin analogues, either LAR or lanreotide. Besides the different drug used, the duration of treatment also plays an important role on the shrinkage magnitude. In a homogeneous cohort of 56 patients treated with LAR only and continuously for 24 months, we noted an even more sustained effect on tumor shrinkage: overall, tumor volume decreased by 68.1±16.5% using dosages up-titrated to 40 mg every 28 days.
Despite this evidence, there is still a debate on the use of first-line treatment with somatostatin analogues. Of paramount importance would be the possibility to predict the results of one year treatment early after treatment beginning. Controversy has been reported on the predictive value of initial tumor size, inhibition of GH and IGF-I levels during treatment, and dose or type of the somatostatin analogue used during treatment. We found that percent suppression of IGF-I after 12 months of LAR treatment was the parameter that best predicted the amount of tumor shrinkage after the same period, but did not investigate the results of short-term treatment in the same series.
This observational, analytical, open, retrospective study was designed to evaluate the predictive value of tumor shrinkage, GH and IGF-I suppression after 3 months of Octreotide-LAR (LAR) on tumor shrinkage obtained after 12 months. As secondary parameters we also studied baseline patients profile such as age of diagnosis, gender, estimated disease duration, GH and IGF-I levels and tumor size.
Read the detailed description
From Jan 1st 1995 to December 31st 2006, all files of patients with newly diagnosed active acromegaly out of the 297 patients coming to our Department for acromegaly who received first-line treatment with LAR will be considered for this study.
As our routine procedure, all patients signed an informed consent to approve diagnostic testing, treatment decision, methods for follow-up and data treatment for scientific purposes. This study has been conducted in accordance with the Helsinki II Declaration on human experimentation. This study takes advantage from data collected in a large, prospective study to investigate the effect of first-line surgery or medical therapy (with somatostatin analogues and/or dopamine/agonists) on GH, IGF-I, tumor mass, cardiovascular risk markers, cardiomyopathy, hypertension, metabolic profile and prostate diseases in all the patients coming for a diagnosis of acromegaly in our Department and approved by our Ethical Committee the 14/10/97 (no.60/97).
- Conditions
- Acromegaly
- Being tested
- Octreotide-LAR
- Keywords
- GH, IGF-I, GH-secreting tumors, Octreotide
- Medical subject headings
- Acromegaly
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Octreotide-LARDrug
Also called Sandostatin (Novartis Pharma)
Initial dose is 20 mg every 28 d for three months, then the dose is down-titrated to 10 mg/q28d if GH levels are below 1 ng/ml, up-titrated to 30 mg/q28d if GH levels are above 10 ng/ml and remains to 20 mg/q28 d if GH is between 1-10 ng/ml
| Study group | Role | What they receive |
|---|---|---|
| A | Newly diagnosed active acromegaly out of the 297 patients coming to our Department for acromegaly who received first-line treatment with LAR Receives: Drug: Octreotide-LAR |
What is being measured
The primary outcome is the main question the study is designed to answer.
GH and IGF-I age-normalized levels, percent GH and IGF-I suppression and percent tumor shrinkage after 3 months
Measured: 12 months
Secondary outcomes (1)
baseline age, gender, estimated disease duration, GH and IGF-I levels, tumor size
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2008 (estimated)
- Study startJan 1997
- Primary completionDec 2007
- Study completionDec 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for AcromegalyStudies of the same condition, open and under way.
- More trials run by Federico II UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Investigators
- Annamaria Colao, MD, Principal investigator, University Federico II of Naples
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00616408
- Sponsor's protocol ID
- NeuroendoUnit-8
- Status last verified
- Dec 2007
- First submitted
- 5 Feb 2008
- Last updated
- 15 Feb 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
Colao A, Pivonello R, Auriemma RS, Galdiero M, Savastano S, Lombardi G. Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol. 2007 Nov;157(5):579-87. doi: 10.1530/EJE-07-0383.
PubMed 17984237Mercado M, Borges F, Bouterfa H, Chang TC, Chervin A, Farrall AJ, Patocs A, Petersenn S, Podoba J, Safari M, Wardlaw J; SMS995B2401 Study Group. A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly. Clin Endocrinol (Oxf). 2007 Jun;66(6):859-68. doi: 10.1111/j.1365-2265.2007.02825.x. Epub 2007 Apr 25.
PubMed 17465997Resmini E, Dadati P, Ravetti JL, Zona G, Spaziante R, Saveanu A, Jaquet P, Culler MD, Bianchi F, Rebora A, Minuto F, Ferone D. Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient. J Clin Endocrinol Metab. 2007 May;92(5):1592-9. doi: 10.1210/jc.2006-2084. Epub 2007 Feb 20.
PubMed 17311860Colao A, Pivonello R, Auriemma RS, Briganti F, Galdiero M, Tortora F, Caranci F, Cirillo S, Lombardi G. Predictors of tumor shrinkage after primary therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Metab. 2006 Jun;91(6):2112-8. doi: 10.1210/jc.2005-2110. Epub 2006 Mar 14.
PubMed 16537687Cozzi R, Montini M, Attanasio R, Albizzi M, Lasio G, Lodrini S, Doneda P, Cortesi L, Pagani G. Primary treatment of acromegaly with octreotide LAR: a long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage. J Clin Endocrinol Metab. 2006 Apr;91(4):1397-403. doi: 10.1210/jc.2005-2347. Epub 2006 Jan 31.
PubMed 16449332Sheppard MC. Primary medical therapy for acromegaly. Clin Endocrinol (Oxf). 2003 Apr;58(4):387-99. doi: 10.1046/j.1365-2265.2003.01734.x.
PubMed 12641619Colao A, Pivonello R, Auriemma RS, Galdiero M, Savastano S, Grasso LF, Lombardi G. Growth hormone-secreting tumor shrinkage after 3 months of octreotide-long-acting release therapy predicts the response at 12 months. J Clin Endocrinol Metab. 2008 Sep;93(9):3436-42. doi: 10.1210/jc.2008-0424. Epub 2008 Jul 1.
PubMed 18593770
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predictive Value of 3 Months Results on 12 Months Tumor Shrinkage After First-Line Octreotide-LAR Therapy in Patients With Acromegaly
- ClinicalTrials.gov ID
- NCT00616408
- Acronym / sponsor ID
- NeuroendoUnit-8
- Conditions
- Acromegaly
- Keywords
- GH, IGF-I, GH-secreting tumors, Octreotide
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Study start
- Jan 1997
- Primary completion
- Dec 2007 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 15 Feb 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In the last two decades, somatostatin analogs have become a cornerstone of medical therapy for acromegaly. One year of treatment with octreotide-LAR (LAR) controls GH and IGF-I excess in 54% and 63% of unselected patients, with an increasing proportion of subjects achieving IGF-I normalization prolonging the treatment. Clinically significant tumor shrinkage (20-30% vs. baseline) has also been reported, with a higher proportion in patients treated first-line [231 of 448 patients (52%)] than in those treated after surgery and/or radiotherapy [52 of 248 patients (21%)]. The highest rate of clinically significant shrinkage (>20%) occurred in patients treated first-line with LAR (80%) as compared to the short-lasting octreotide formulation (50%) or lanreotide slow-release formulation (35%. In 99 de novo patients with acromegaly, we recently reported control of GH levels in 57.6%, of IGF-I levels in 45.5% and a greater than 50% tumor shrinkage in 44.4% after 12 months of first-line treatment with somatostatin analogues, either LAR or lanreotide. Besides the different drug used, the duration of treatment also plays an important role on the shrinkage magnitude. In a homogeneous cohort of 56 patients treated with LAR only and continuously for 24 months, we noted an even more sustained effect on tumor shrinkage: overall, tumor volume decreased by 68.1±16.5% using dosages up-titrated to 40 mg every 28 days.
Despite this evidence, there is still a debate on the use of first-line treatment with somatostatin analogues. Of paramount importance would be the possibility to predict the results of one year treatment early after treatment beginning. Controversy has been reported on the predictive value of initial tumor size, inhibition of GH and IGF-I levels during treatment, and dose or type of the somatostatin analogue used during treatment. We found that percent suppression of IGF-I after 12 months of LAR treatment was the parameter that best predicted the amount of tumor shrinkage after the same period, but did not investigate the results of short-term treatment in the same series.
This observational, analytical, open, retrospective study was designed to evaluate the predictive value of tumor shrinkage, GH and IGF-I suppression after 3 months of Octreotide-LAR (LAR) on tumor shrinkage obtained after 12 months. As secondary parameters we also studied baseline patients profile such as age of diagnosis, gender, estimated disease duration, GH and IGF-I levels and tumor size.
Detailed description
From Jan 1st 1995 to December 31st 2006, all files of patients with newly diagnosed active acromegaly out of the 297 patients coming to our Department for acromegaly who received first-line treatment with LAR will be considered for this study.
As our routine procedure, all patients signed an informed consent to approve diagnostic testing, treatment decision, methods for follow-up and data treatment for scientific purposes. This study has been conducted in accordance with the Helsinki II Declaration on human experimentation. This study takes advantage from data collected in a large, prospective study to investigate the effect of first-line surgery or medical therapy (with somatostatin analogues and/or dopamine/agonists) on GH, IGF-I, tumor mass, cardiovascular risk markers, cardiomyopathy, hypertension, metabolic profile and prostate diseases in all the patients coming for a diagnosis of acromegaly in our Department and approved by our Ethical Committee the 14/10/97 (no.60/97).
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | – | Drug: Octreotide-LARNewly diagnosed active acromegaly out of the 297 patients coming to our Department for acromegaly who received first-line treatment with LAR |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Newly diagnosed patients with acromegaly treated first-line with octreotide-LAR
Key inclusion criteria (1 listed)
- No previous treatment for acromegaly
Key exclusion criteria (3 listed)
- primary surgery
- concomitant hyperprolactinemia requiring combined somatostatin analogues and dopamine-agonist treatment
- primary treatment with lanreotide
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Octreotide-LARAlso: Sandostatin (Novartis Pharma)Initial dose is 20 mg every 28 d for three months, then the dose is down-titrated to 10 mg/q28d if GH levels are below 1 ng/ml, up-titrated to 30 mg/q28d if GH levels are above 10 ng/ml and remains to 20 mg/q28 d if GH is between 1-10 ng/ml | Drug | A |
Primary outcome
GH and IGF-I age-normalized levels, percent GH and IGF-I suppression and percent tumor shrinkage after 3 months
Time frame: 12 months
1 secondary outcome
baseline age, gender, estimated disease duration, GH and IGF-I levels, tumor size
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2008.
- Results publication: PubMed 17984237Colao A, Pivonello R, Auriemma RS, Galdiero M, Savastano S, Lombardi G. Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol. 2007 Nov;157(5):579-87. doi: 10.1530/EJE-07-0383.
- Results publication: PubMed 17465997Mercado M, Borges F, Bouterfa H, Chang TC, Chervin A, Farrall AJ, Patocs A, Petersenn S, Podoba J, Safari M, Wardlaw J; SMS995B2401 Study Group. A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly. Clin Endocrinol (Oxf). 2007 Jun;66(6):859-68. doi: 10.1111/j.1365-2265.2007.02825.x. Epub 2007 Apr 25.
- Results publication: PubMed 17311860Resmini E, Dadati P, Ravetti JL, Zona G, Spaziante R, Saveanu A, Jaquet P, Culler MD, Bianchi F, Rebora A, Minuto F, Ferone D. Rapid pituitary tumor shrinkage with dissociation between antiproliferative and antisecretory effects of a long-acting octreotide in an acromegalic patient. J Clin Endocrinol Metab. 2007 May;92(5):1592-9. doi: 10.1210/jc.2006-2084. Epub 2007 Feb 20.
- Results publication: PubMed 16537687Colao A, Pivonello R, Auriemma RS, Briganti F, Galdiero M, Tortora F, Caranci F, Cirillo S, Lombardi G. Predictors of tumor shrinkage after primary therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Metab. 2006 Jun;91(6):2112-8. doi: 10.1210/jc.2005-2110. Epub 2006 Mar 14.
- Results publication: PubMed 16449332Cozzi R, Montini M, Attanasio R, Albizzi M, Lasio G, Lodrini S, Doneda P, Cortesi L, Pagani G. Primary treatment of acromegaly with octreotide LAR: a long-term (up to nine years) prospective study of its efficacy in the control of disease activity and tumor shrinkage. J Clin Endocrinol Metab. 2006 Apr;91(4):1397-403. doi: 10.1210/jc.2005-2347. Epub 2006 Jan 31.
- Results publication: PubMed 12641619Sheppard MC. Primary medical therapy for acromegaly. Clin Endocrinol (Oxf). 2003 Apr;58(4):387-99. doi: 10.1046/j.1365-2265.2003.01734.x.
- Derived from this study: PubMed 18593770Colao A, Pivonello R, Auriemma RS, Galdiero M, Savastano S, Grasso LF, Lombardi G. Growth hormone-secreting tumor shrinkage after 3 months of octreotide-long-acting release therapy predicts the response at 12 months. J Clin Endocrinol Metab. 2008 Sep;93(9):3436-42. doi: 10.1210/jc.2008-0424. Epub 2008 Jul 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Annamaria Colao, MD principal investigator
University Federico II of Naples
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acromegaly, run by Federico II University at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Feb 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GH and IGF-I age-normalized levels, percent GH and IGF-I suppression and percent tumor shrinkage after 3 months (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00616408, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2008.