Multicenter Evaluation of the Effect of Upfront Radiosurgery on Residual Growth Hormone-secreting Pituitary Adenoma (MERGE)

February 28, 2018 updated by: Samsung Medical Center

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

90

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

      1. random growth hormone level < 2.5 ug/L
      2. normalization of age-matched insulin growth factor-1 level

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: intervention
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
Radiation: Gamma knife radiosurgery
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.
Drug: Lanreotide 60Mg Solution for Injection
Lanreotide injection.
Active Comparator: control
Without radiosurgery, standard medical therapy (Lanreotide 60Mg Solution for Injection) same with interventional group is applied
Drug: Lanreotide 60Mg Solution for Injection
Lanreotide injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
at 2 year after initial enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
tumor size
Time Frame: 1 year interval
maximum diameter of tumor
1 year interval
drug requirement dosage
Time Frame: at 3 months after initial enrollment and 6 months thereafter for 2 years
daily total dose requirement (multiplied dose per injection by number of injections)
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
radiation induced and drug related side effects
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

modified Rankin scale; lower values represent a better outcome as followings: 0 - No symptoms.

  1. - No significant disability. Able to carry out all usual activities, despite some symptoms.
  2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
  3. - Moderate disability. Requires some help, but able to walk unassisted.
  4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
  5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
  6. - Dead.
at 3 months after initial enrollment and 6 months thereafter for 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Samsung Medical Center

Investigators

  • Principal Investigator: Doo0Sik Kong, MD,Ph.D, Samsung Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

March 1, 2018

Primary Completion (Anticipated)

June 30, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

February 1, 2018

First Submitted That Met QC Criteria

February 13, 2018

First Posted (Actual)

February 20, 2018

Study Record Updates

Last Update Posted (Actual)

March 1, 2018

Last Update Submitted That Met QC Criteria

February 28, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SMC 2017-11-091-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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