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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years - 70 Years
Gender	All

More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03439709
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Samsung Medical Center
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Doo0Sik Kong, MD,Ph.D
Principal Investigator Affiliation	Samsung Medical Center
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	Korea, Republic of
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Acromegaly Due to Pituitary Adenoma

Additional Details

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.

Arms & Interventions

Arms

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

Active Comparator: control

Without radiosurgery, standard medical therapy (Lanreotide 60Mg Solution for Injection) same with interventional group is applied

Interventions

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.

Contact a Trial Team

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