Acromegaly Due to Pituitary AdenomaPhase 3MERGENCT03439709
Multicenter Evaluation of the Effect of Upfront Radiosurgery on Residual Growth Hormone-secreting Pituitary Adenoma
A Phase 3 study testing Gamma knife radiosurgery and Lanreotide 60Mg Solution for Injection in people with Acromegaly Due to Pituitary Adenoma, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
In this study, the investigators hypothesize that upfront gamma knife radiosurgery with drug therapy is superior in the treatment of growth hormone-secreting pituitary tumors after primary surgical treatment compared with the drug therapy alone. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Acromegaly Due to Pituitary Adenoma
- What is being tested?
- Gamma knife radiosurgery and Lanreotide 60Mg Solution for Injection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteSouth Korea
- Study dates
- 1 Mar 2018to 31 Dec 2022
- Phase
- Phase 3
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Among patients with acromegaly due to growth hormone secreting pituitary adenoma who underwent primary surgical resection, patients who fail to achieve endocrinologic remission at 3 months after surgery.
- On brain MRI scan at 3months after surgery, residual tumor is confirmed by clinicians
- the definition of endocrinologic remission
- random growth hormone level < 2.5 ug/L
- normalization of age-matched insulin growth factor-1 level
Who cannot join
- patients with contraindication of stereotactic radiosurgery; e.g. pregnancy or planning pregnancy, or claustrophobia
- recurrent pituitary adenoma
- limited life expectancy due to systemic disease; e.g. malignant tumor, genetic disease, and terminal stage of renal or hepatic failure
- disability to clinic visit due to postoperative complications
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Multicenter Evaluation of the Effect of Upfront Radiosurgery on Residual Growth Hormone-secreting Pituitary Adenoma From an Endocrinological Point of View (MERGE Study): a Randomized, Phase 3 Trial
In this study, the investigators hypothesize that upfront gamma knife radiosurgery with drug therapy is superior in the treatment of growth hormone-secreting pituitary tumors after primary surgical treatment compared with the drug therapy alone. This study can provide useful clinical information in the treatment of patients with acromegaly.
Read the detailed description
Acromegaly is often caused by growth hormone (GH)-secreting pituitary adenoma and causes anatomic changes in the body and various metabolic disorders caused by increased GH and insulin-like growth factor-1 (IGF1). Surgical treatment of pituitary tumors is the preferred standard of care, but only 40-70% of patients can be treated with surgical treatment alone. In many cases, complete resection of the tumor is not possible and the hormone imbalance persists after surgery. After surgical treatment, several additional treatments are needed to prevent hypersecretion of GH and to normalize blood levels of IGF-1.
As first-line treatment after surgical resection, there are typically drug therapy and radiation therapy. The most common used drugs are octreotide and lanreotide, which are growth hormone analogues. However, according to the recent guideline, the endocrine remission rate obtained from post-operative drug therapy is only 17-35%. Although clinical trials are underway for new drugs, the burden of expensive drug costs, recurrence during drug withdrawal, and drug side effects remains major drawbacks. There is a need for therapeutic intervention to reduce the dose and duration of therapy, to prevent tumor recurrence, and to achieve rapid endocrinologic remission.
Stereotactic radiosurgery (SRS), such as gamma knife radiosurgery, has been actively introduced worldwide to control residual pituitary tumors and has been applied to more than 200 cases of intractable acromegaly. The effect of SRS on endocrine remission in patients who did not receive endocrine therapy was confirmed in the literature. In a study of 136 patients who underwent preoperative radiotherapy followed by more than 5 years of follow-up, 65.4% of patients reported endocrine remission. According to the recently published meta-analysis, SRS showed 93-100% tumor growth control and size reduction within 5 to 10 years after surgery. The endocrinologic remission rate was reported to be 40-60% at 5 years.
To date, SRS has been recommended for the treatment of growth hormone - secreting pituitary tumors in cases where surgical removal is not feasible from the beginning or if drug treatment fails after surgical removal. Only the retrospective study of SRS was performed and no prospective study was conducted at all. However, many institutions already prefer preemptive SRS treatment for residual tumor after surgery and have been practiced in many patients. Therefore, prospective clinical trials are needed to establish the basis for upfront SRS and establish the treatment strategy for patients who do not have endocrine remission after surgical treatment of GH secretory pituitary tumor.
- Conditions
- Acromegaly Due to Pituitary Adenoma
- Being tested
- Gamma knife radiosurgery, Lanreotide 60Mg Solution for Injection
- Keywords
- acromegaly, pituitary adenoma, gamma knife radiosurgery, adjuvant treatment
- Medical subject headings
- Growth Hormone-Secreting Pituitary Adenoma, Acromegaly, Pituitary Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gamma knife radiosurgeryRadiation
Minimum 25 Gy of marginal dose is applied for residual tumor or resection cavity. Depending on the size of tumor, the dose can be varied.
Lanreotide 60Mg Solution for InjectionDrug
Lanreotide injection.
| Study group | Role | What they receive |
|---|---|---|
| intervention | Experimental | Gamma knife radiosurgery (Leksell Gamma Knife, Elekta AB, Stockholm, Sweden) is used for intervention. Administration of standard medical therapy using Lanreotide 60 mg concurrently starts with radiosurgery Receives: Radiation: Gamma knife radiosurgery; Drug: Lanreotide 60Mg Solution for Injection |
| control | Active comparator | Without radiosurgery, standard medical therapy (Lanreotide 60Mg Solution for Injection) same with interventional group is applied Receives: Drug: Lanreotide 60Mg Solution for Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
endocrinologic remission
Achieving random growth hormone level below 2.5 ug/L and normalization of insulin-growth factor-1 level
Measured: at 2 year after initial enrollment
Secondary outcomes (4)
tumor size
maximum diameter of tumor
Measured: 1 year interval
drug requirement dosage
daily total dose requirement (multiplied dose per injection by number of injections)
Measured: at 3 months after initial enrollment and 6 months thereafter for 2 years
side effect
radiation induced and drug related side effects
Measured: at 3 months after initial enrollment and 6 months thereafter for 2 years
performance status
modified Rankin scale; lower values represent a better outcome as followings: 0 - No symptoms.
- - No significant disability. Able to carry out all usual activities, despite some symptoms.
- - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
- - Moderate disability. Requires some help, but able to walk unassisted.
- - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
- - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
- - Dead.
Measured: at 3 months after initial enrollment and 6 months thereafter for 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2018
- Study start1 Mar 2018 (estimated)
- Primary completion30 Jun 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Acromegaly Due to Pituitary AdenomaStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The patients with acromegaly due to growth hormone secreting pituitary adenoma who receive primary surgical resection and fail to achieve endocrinologic remission at 3 months after surgical resection are enrolled. They are devided into two groups; One consists of patients underwent upfront stereotactic radiosurgery combinated with standard drug therapy, and another group consists of patients receiving only standard drug therapy.
- Masking
- None (open label)
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Doo0Sik Kong, MD,Ph.D, Principal investigator, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03439709
- Sponsor's protocol ID
- SMC 2017-11-091-002
- Acronym
- MERGE
- Status last verified
- Feb 2018
- First submitted
- 1 Feb 2018
- Last updated
- 1 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Gheorghiu ML. Updates in outcomes of stereotactic radiation therapy in acromegaly. Pituitary. 2017 Feb;20(1):154-168. doi: 10.1007/s11102-016-0783-5.
PubMed 28210908Lee CC, Vance ML, Xu Z, Yen CP, Schlesinger D, Dodson B, Sheehan J. Stereotactic radiosurgery for acromegaly. J Clin Endocrinol Metab. 2014 Apr;99(4):1273-81. doi: 10.1210/jc.2013-3743. Epub 2014 Jan 28.
PubMed 24471574Shin SS, Tormenti MJ, Paluzzi A, Rothfus WE, Chang YF, Zainah H, Fernandez-Miranda JC, Snyderman CH, Challinor SM, Gardner PA. Endoscopic endonasal approach for growth hormone secreting pituitary adenomas: outcomes in 53 patients using 2010 consensus criteria for remission. Pituitary. 2013 Dec;16(4):435-44. doi: 10.1007/s11102-012-0440-6.
PubMed 23179961Giustina A, Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A, van der Lely AJ, Strasburger CJ, Lamberts SW, Ho KK, Casanueva FF, Melmed S; Acromegaly Consensus Group. Expert consensus document: A consensus on the medical treatment of acromegaly. Nat Rev Endocrinol. 2014 Apr;10(4):243-8. doi: 10.1038/nrendo.2014.21. Epub 2014 Feb 25.
PubMed 24566817Hazer DB, Isik S, Berker D, Guler S, Gurlek A, Yucel T, Berker M. Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria. J Neurosurg. 2013 Dec;119(6):1467-77. doi: 10.3171/2013.8.JNS13224. Epub 2013 Sep 27.
PubMed 24074496Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA; Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Nov;99(11):3933-51. doi: 10.1210/jc.2014-2700. Epub 2014 Oct 30.
PubMed 25356808
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Evaluation of the Effect of Upfront Radiosurgery on Residual Growth Hormone-secreting Pituitary Adenoma From an Endocrinological Point of View (MERGE Study): a Randomized, Phase 3 Trial
- ClinicalTrials.gov ID
- NCT03439709
- Acronym / sponsor ID
- MERGE / SMC 2017-11-091-002
- Conditions
- Acromegaly Due to Pituitary Adenoma
- Keywords
- acromegaly, pituitary adenoma, gamma knife radiosurgery, adjuvant treatment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 90 participants (estimated)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- 1 Mar 2018 (estimated)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 20 Feb 2018 (actual)
- 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 this study, the investigators hypothesize that upfront gamma knife radiosurgery with drug therapy is superior in the treatment of growth hormone-secreting pituitary tumors after primary surgical treatment compared with the drug therapy alone. This study can provide useful clinical information in the treatment of patients with acromegaly.
Detailed description
Acromegaly is often caused by growth hormone (GH)-secreting pituitary adenoma and causes anatomic changes in the body and various metabolic disorders caused by increased GH and insulin-like growth factor-1 (IGF1). Surgical treatment of pituitary tumors is the preferred standard of care, but only 40-70% of patients can be treated with surgical treatment alone. In many cases, complete resection of the tumor is not possible and the hormone imbalance persists after surgery. After surgical treatment, several additional treatments are needed to prevent hypersecretion of GH and to normalize blood levels of IGF-1.
As first-line treatment after surgical resection, there are typically drug therapy and radiation therapy. The most common used drugs are octreotide and lanreotide, which are growth hormone analogues. However, according to the recent guideline, the endocrine remission rate obtained from post-operative drug therapy is only 17-35%. Although clinical trials are underway for new drugs, the burden of expensive drug costs, recurrence during drug withdrawal, and drug side effects remains major drawbacks. There is a need for therapeutic intervention to reduce the dose and duration of therapy, to prevent tumor recurrence, and to achieve rapid endocrinologic remission.
Stereotactic radiosurgery (SRS), such as gamma knife radiosurgery, has been actively introduced worldwide to control residual pituitary tumors and has been applied to more than 200 cases of intractable acromegaly. The effect of SRS on endocrine remission in patients who did not receive endocrine therapy was confirmed in the literature. In a study of 136 patients who underwent preoperative radiotherapy followed by more than 5 years of follow-up, 65.4% of patients reported endocrine remission. According to the recently published meta-analysis, SRS showed 93-100% tumor growth control and size reduction within 5 to 10 years after surgery. The endocrinologic remission rate was reported to be 40-60% at 5 years.
To date, SRS has been recommended for the treatment of growth hormone - secreting pituitary tumors in cases where surgical removal is not feasible from the beginning or if drug treatment fails after surgical removal. Only the retrospective study of SRS was performed and no prospective study was conducted at all. However, many institutions already prefer preemptive SRS treatment for residual tumor after surgery and have been practiced in many patients. Therefore, prospective clinical trials are needed to establish the basis for upfront SRS and establish the treatment strategy for patients who do not have endocrine remission after surgical treatment of GH secretory pituitary tumor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The patients with acromegaly due to growth hormone secreting pituitary adenoma who receive primary surgical resection and fail to achieve endocrinologic remission at 3 months after surgical resection are enrolled. They are devided into two groups; One consists of patients underwent upfront stereotactic radiosurgery combinated with standard drug therapy, and another group consists of patients receiving only standard drug therapy.
| Arm | Type | Receives |
|---|---|---|
| intervention | Experimental | Radiation: Gamma knife radiosurgery, Drug: Lanreotide 60Mg Solution for InjectionGamma knife radiosurgery (Leksell Gamma Knife, Elekta AB, Stockholm, Sweden) is used for intervention. Administration of standard medical therapy using Lanreotide 60 mg concurrently starts with radiosurgery |
| control | Active comparator | Drug: Lanreotide 60Mg Solution for InjectionWithout radiosurgery, standard medical therapy (Lanreotide 60Mg Solution for Injection) same with interventional group is applied |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Among patients with acromegaly due to growth hormone secreting pituitary adenoma who underwent primary surgical resection, patients who fail to achieve endocrinologic remission at 3 months after surgery.
- On brain MRI scan at 3months after surgery, residual tumor is confirmed by clinicians
Key exclusion criteria (4 listed)
- patients with contraindication of stereotactic radiosurgery; e.g. pregnancy or planning pregnancy, or claustrophobia
- recurrent pituitary adenoma
- limited life expectancy due to systemic disease; e.g. malignant tumor, genetic disease, and terminal stage of renal or hepatic failure
- disability to clinic visit due to postoperative complications
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 |
|---|---|---|
| Gamma knife radiosurgeryMinimum 25 Gy of marginal dose is applied for residual tumor or resection cavity. Depending on the size of tumor, the dose can be varied. | Radiation | intervention |
| Lanreotide 60Mg Solution for InjectionLanreotide injection. | Drug | control, intervention |
Primary outcome
endocrinologic remission
Time frame: at 2 year after initial enrollment
Achieving random growth hormone level below 2.5 ug/L and normalization of insulin-growth factor-1 level
4 secondary outcomes
tumor size
Time frame: 1 year interval
drug requirement dosage
Time frame: at 3 months after initial enrollment and 6 months thereafter for 2 years
side effect
Time frame: at 3 months after initial enrollment and 6 months thereafter for 2 years
performance status
Time frame: at 3 months after initial enrollment and 6 months thereafter for 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2018.
- Background: PubMed 28210908Gheorghiu ML. Updates in outcomes of stereotactic radiation therapy in acromegaly. Pituitary. 2017 Feb;20(1):154-168. doi: 10.1007/s11102-016-0783-5.
- Background: PubMed 24471574Lee CC, Vance ML, Xu Z, Yen CP, Schlesinger D, Dodson B, Sheehan J. Stereotactic radiosurgery for acromegaly. J Clin Endocrinol Metab. 2014 Apr;99(4):1273-81. doi: 10.1210/jc.2013-3743. Epub 2014 Jan 28.
- Background: PubMed 23179961Shin SS, Tormenti MJ, Paluzzi A, Rothfus WE, Chang YF, Zainah H, Fernandez-Miranda JC, Snyderman CH, Challinor SM, Gardner PA. Endoscopic endonasal approach for growth hormone secreting pituitary adenomas: outcomes in 53 patients using 2010 consensus criteria for remission. Pituitary. 2013 Dec;16(4):435-44. doi: 10.1007/s11102-012-0440-6.
- Background: PubMed 24566817Giustina A, Chanson P, Kleinberg D, Bronstein MD, Clemmons DR, Klibanski A, van der Lely AJ, Strasburger CJ, Lamberts SW, Ho KK, Casanueva FF, Melmed S; Acromegaly Consensus Group. Expert consensus document: A consensus on the medical treatment of acromegaly. Nat Rev Endocrinol. 2014 Apr;10(4):243-8. doi: 10.1038/nrendo.2014.21. Epub 2014 Feb 25.
- Background: PubMed 24074496Hazer DB, Isik S, Berker D, Guler S, Gurlek A, Yucel T, Berker M. Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria. J Neurosurg. 2013 Dec;119(6):1467-77. doi: 10.3171/2013.8.JNS13224. Epub 2013 Sep 27.
- Background: PubMed 25356808Katznelson L, Laws ER Jr, Melmed S, Molitch ME, Murad MH, Utz A, Wass JA; Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014 Nov;99(11):3933-51. doi: 10.1210/jc.2014-2700. Epub 2014 Oct 30.
- Individual participant dataSharing planned: Undecided
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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.
Doo0Sik Kong, MD,Ph.D principal investigator
Samsung Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Gamma knife radiosurgery and Lanreotide 60Mg Solution for Injection in people with Acromegaly Due to Pituitary Adenoma, run by Samsung Medical Center at 1 site in South Korea.
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 5 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 1 Mar 2018. 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 South Korea. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Doo-Sik Kong, MD,Ph.D (+82-2-3410-0732, doosik.kong@samsung.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
endocrinologic remission (time frame: at 2 year after initial enrollment). 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 NCT03439709, which also lists 6 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 1 Mar 2018.