Radiosurgical Hypophysectomy for Bone Metasteses Pain

A Pilot Study of Stereotactic Radiosurgical Hypophysectomy for Intractable Pain From Bone Metastases

This research is being done to see if a delivery of a single high dose of radiation therapy to a small area of the pituitary gland and pituitary stalk in a highly precise manner may be helpful in reducing intractable pain from bone metastases.

Study Overview

• Status: Recruiting
• Conditions: Bone Metastases
• Intervention / Treatment: Radiation: radiosurgical hypophysectomy

Detailed Description

Although not currently standard of care, small series suggest both safety and efficacy of radiosurgical hypophysectomy in reducing cancer pain from bone metastases. In spite of the demonstrated feasibility in meeting normal tissue constraints and preliminary data suggestive of both safety and efficacy, radiosurgical hypophysectomy is rarely performed in clinical practice, and many radiation oncologists are not even aware of its potential to reduce intractable cancer pain. This is likely because, to date, well-designed prospective studies have not been performed to further explore both the safety and efficacy of the intervention. This single arm pilot study is designed to fill that void. If successful, the investigators plan to utilize the data to support the proposal of a larger scale follow-up clinical trial.

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kristin Redmond, MD; Phone Number: 410-614-1642; Email: kjanson3@jhmi.edu
• Study Contact Backup: Name: Danielle Wendler, RN; Phone Number: (410) 502-9243; Email: dschul15@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • The Sidney Kimmel Comprehsensive Cancer Center at Johns Hopkins
      • Sub-Investigator: Lawrence Kleinberg, MD
      • Sub-Investigator: Roberto Salvatori, MD
      • Sub-Investigator: Thomas Smith, MD
      • Sub-Investigator: Michael Lim, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Cytologic proof of malignancy
2. Radiographic evidence of bone metastases
3. Intractable pain uncontrolled by opioids, medical management, injections/ablation or surgical intervention that would be difficult to address with conventional radiation therapy or other standard options and is limiting the patient's function and quality of life. Intractable pain will be defined as a visual analogue score of at least 4.
4. Definitive radiographic progression of osseous and/or visceral metastases on standard staging scans (CT, MRI, bone scan, PET scan or any other standard of care imaging) performed within the last 3 months in spite of standard oncologic interventions and/or inability to tolerate standard oncologic interventions
5. Life expectancy at least 4 weeks
6. Age≥ 18 years
7. Patients of childbearing potential (male or female) must practice adequate contraception due to possible harmful effects of radiation therapy on an unborn child
8. Patient must have the ability to understand and the willingness to sign a written informed consent document
9. All patients must be informed of the investigational nature of this study and must be given written informed consent in accordance with institutional and federal guidelines

Exclusion Criteria:

1. Prior brain radiation
2. Patients must not have a serious medical or psychiatric illness that would, in the opinion of the treating physician prevent informed consent or completion of protocol treatment
3. Isolated localized pain amenable to focal radiation therapy, or pain well controlled by opioids, medical management, injections/ablation or surgical intervention
4. Malignancies being managed with curative intent
5. Life expectancy <4 weeks
6. The tumor amenable to curative management

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ResearchTreatment Plan; Patients will be treated to a dose of 150 Gy in a single fraction. All patients will undergo CT simulation with 1 mm slices as well as MRI simulation including at least high resolution 1 mm slice T1 weighted MRI. They will be treated in a supine position using an aquaplast mask system for immobilization.	Radiation: radiosurgical hypophysectomy; Patients will be treated to a dose of 150 Gy in a single fraction. All patients will undergo CT simulation with 1 mm slices as well as MRI simulation including at least high resolution 1 mm slice T1 weighted MRI. They will be treated in a supine position using an aquaplast mask system for immobilization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Intensity of Bone Pain	To estimate the rate of clinically meaningful decrease in diffuse osseous pain following radiosurgical hypophysectomy at 4 weeks following completion of radiosurgical hypophysectomy	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of change of disease spread	To estimate the rate of clinically meaningful decrease in diffuse osseous pain following radiosurgical hypophysectomy	Up to 100 weeks following completion of radiosurgical hypophysectomy
Rate of Change of Quality of Life	To estimate the rate of clinically meaningful increase in patient reported quality of life following radiosurgical hypophysectomy	Up to 100 weeks following completion of radiosurgical hypophysectomy
Rate of change in opioid use	To estimate the rate of reduction in opioid utilization following radiosurgical hypophysectomy	Up to 100 weeks following completion of radiosurgical hypophysectomy
Rate of biochemical endocrinopathy	To estimate the rate of biochemical endocrinopathy following radiosurgical hypophysectomy	Up to 100 weeks following completion of radiosurgical hypophysectomy
Rate of change of optic nueropathy	To estimate the risk of radiation induced optic neuropathy following radiosurgical hypophysectomy	Up to 100 weeks following completion of radiosurgical hypophysectomy
Rate of change of neurologic toxicity	To estimate the radiation-associated acute and long term neurologic toxicity of radiosurgical hypophysectomy	Up to 100 weeks following completion of radiosurgical hypophysectomy
Rate of change of insipidus diabetes	To estimate the rate of diabetes insipidus following radiosurgical hypophysectomy	Up to 100 weeks following completion of radiosurgical hypophysectomy
Rate of change in costs	To estimate the cost effectiveness of radiosurgical hypophysectomy	Up to 100 weeks following completion of radiosurgical hypophysectomy
Rate of change of cortisol	To estimate the relationship between pain response and cortisol levels	Up to 100 weeks following completion of radiosurgical hypophysectomy
Rate of change of pain with respect to hormones	To estimate the rate of pain response in hormonally active and non-hormonally active tumors	Up to 100 weeks following completion of radiosurgical hypophysectomy
Rate of change of pain with respect to morphine	To estimate the rate of pain response in morphine sensitive and morphine insensitive tumors	Up to 100 weeks following completion of radiosurgical hypophysectomy

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Accuray Incorporated
• Investigators: Principal Investigator: Kristin Redmond, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2018
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 8, 2017
• First Submitted That Met QC Criteria: December 13, 2017
• First Posted (Actual): December 19, 2017

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: J17181; IRB00158648 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No