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

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ClinicalTrials.gov Identifier: NCT03439709
Recruitment Status : Not yet recruiting
First Posted : February 20, 2018
Last Update Posted : March 1, 2018
Sponsor:
Information provided by (Responsible Party):
Samsung Medical Center

Tracking Information
First Submitted Date  ICMJE February 1, 2018
First Posted Date  ICMJE February 20, 2018
Last Update Posted Date March 1, 2018
Estimated Study Start Date  ICMJE March 1, 2018
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 28, 2018)
  • tumor size [ Time Frame: 1 year interval ]
    maximum diameter of tumor
  • 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)
  • side effect [ Time Frame: at 3 months after initial enrollment and 6 months thereafter for 2 years ]
    radiation induced and drug related side effects
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2018)
  • tumor size [ Time Frame: 1 year interval ]
    maximum diameter of tumor
  • drug requirement dosage [ Time Frame: at 3 months after initial enrollment and 6 months thereafter for 2 years ]
    daily total dose requirment (multiplied dose per injection by number of injections)
  • side effect [ Time Frame: at 3 months after initial enrollment and 6 months thereafter for 2 years ]
    radiation induced and drug related side effects
  • 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Multicenter Evaluation of the Effect of Upfront Radiosurgery on Residual Growth Hormone-secreting Pituitary Adenoma
Official Title  ICMJE 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
Brief 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. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Masking Description:
Technically, the procedure of gamma knife radiosurgery includes fixating stereotactic frame on the head of patients. Therefore, It is not possible to keep masking for participants and other investigators.
Primary Purpose: Treatment
Condition  ICMJE Acromegaly Due to Pituitary Adenoma
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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
    Interventions:
    • Radiation: Gamma knife radiosurgery
    • Drug: Lanreotide 60Mg Solution for Injection
  • Active Comparator: control
    Without radiosurgery, standard medical therapy (Lanreotide 60Mg Solution for Injection) same with interventional group is applied
    Intervention: Drug: Lanreotide 60Mg Solution for Injection
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 13, 2018)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date June 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Doo-Sik Kong, MD,Ph.D +82-2-3410-0732 doosik.kong@samsung.com
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03439709
Other Study ID Numbers  ICMJE SMC 2017-11-091-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Samsung Medical Center
Study Sponsor  ICMJE Samsung Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Doo0Sik Kong, MD,Ph.D Samsung Medical Center
PRS Account Samsung Medical Center
Verification Date February 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP