RAD0408: A Phase II Study of Spinal Radiosurgery

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Completed
• CT.gov ID: NCT00573872
• Collaborator: Health Services Foundation (Other), The Kirklin Clinic at Acton Road (Other)
• Enrollment: 43
• Location: 1
• Arm: 1
• Actual Duration (Months): 137
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

Phase I of the study (motion and quality assurance [QA] study) is being used to determine intrafraction target motion and define quality assurance procedures for single fraction spinal radiosurgery. The Phase II portion of the study is being used to estimate the palliative response (pain or relief of neurologic symptoms) and local control for single fraction radiosurgery delivered with TomoTherapy and to assess the acute and late toxicity of spinal radiosurgery.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm; Arteriovenous Malformations	Radiation: Radiosurgery	N/A

Detailed Description

Optimal radiation plan is generated that treats the tumor (CTV) and spares normal tissue, especially the spinal cord. Motion and QA study will determine intrafraction motion for phase II portion of the study.

Dose prescription to tumor is based upon maximal dose received by 0.5 cc of spinal cord and whether patient has had prior radiation therapy to that area:

Phase I - Motion and QA Study: 20-25 Gy in 5 fractions/10-20 patients/previous RT = <50% CTV dose/No previous RT = <80% CTV dose.

Phase II - 9-24 Gy in 1 fraction/30 total in order to have 20 evaluable patients (15 patients with prior RT and 15 without prior RT/previous RT = 8 Gy/No previous RT = 10 Gy.

Motion and QA study will treat CTV to 20-25 Gy in 5 fractions to study intrafraction motion

for QA of single fraction administration. This will define treatment margins for single fraction radiosurgery.

*Previous RT:

• greater than six months since completion of RT

• at least 20 Gy, but no more than 50 Gy

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Spinal Radiosurgery
• Actual Study Start Date: Apr 1, 2005
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Sep 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Spinal Radiosurgery Patients will be fitted in a custom immobilization device. A CT simulation scan will then be performed to pinpoint intended radiosurgery target producing a computer optimized radiation plan to be confirmed by planning radiation physicist. Patient will then be placed in their immobilization device and aligned with the treatment planning position. Patient then receives radiosurgery. Treatment delivery will be divided into components of 3-5Gy with repeat CT based localization in between each of these components. For all patients, a nominal prescription dose of 24Gy will be entered into the tomotherapy cost function. Once the plan that provides maximal spinal sparing has been generated, the plan will be renormalized to produce no more than 8Gy (prior RT) or 10Gy (no prior RT) to 0.5cc of spinal cord by dividing the single fraction treatment into fractions of 3-5Gy.

Radiation: Radiosurgery; Phase I: 20-25 Gy in 5 fractions Phase II: 9-24 GY in 1 fraction

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Palliative Response (Pain or Relief of Neurologic Symptoms) From Single Fraction Radiosurgery Delivered With Tomotherapy [2 years]

   Physician's subjective report of palliative pain relief. The maximal benefit patient received (best response) is reported. Scale is pain described as "worse", "stable", "better", or "completely resolved". In the reporting "better" or "completely resolved" indicates response to treatment.

2. Assess the Acute and Late Toxicity of Spinal Radiosurgery [2 years]

   CTCAE version 3. Acute toxicity will be recorded if toxicity occurs early phase or within 3 months, and late toxicity would be any toxicity that follows those 3 months.

3. Number of Participants With Lack of Tumor Growth at Last Follow-up [2 years]

   Lack of tumor growth by CT or MRI at last follow-up

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. All subjects must have history of histologically confirmed neoplasm or radiographically-diagnosed AVM. Patients without a prior tissue diagnosis but who have a radiographically characteristic lesion are eligible if there is consensus agreement of the diagnosis in the UAB Neuro-oncology Tumor Board.

2. ECOG performance status of less than or equal to 2

3. Age greater than 18

4. Life expectancy greater than 12 weeks

5. Subjects given written informed consent

Exclusion Criteria:

1. Cytotoxic chemotherapy within 7 days of treatment

2. Insufficient recovery from all active toxicities of prior therapies

3. Epidural spinal cord compression requiring immediate neurosurgical decompression. If a patient requires immediate surgery for neurologic compromise, they may still be eligible post operatively if tumor was incompletely resected.

4. Patient is non-ambulatory. Optimization of pretreatment neurologic function with steroids is allowed. Ambulation with assistance of walker or cane is allowed.

5. Patient is pregnant and it is judged by the treating Radiation Oncologist that spinal radiosurgery would place the fetus in unacceptable danger.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham/The Kirklin Clinic at Acton Road	Birmingham	Alabama	United States	35233

Sponsors and Collaborators

• University of Alabama at Birmingham
• Health Services Foundation
• The Kirklin Clinic at Acton Road

Investigators

• Principal Investigator: John B. Fiveash, M.D., University of Alabama at Birmingham

Study Documents (Full-Text)

None provided.

More Information

Publications

• Abbatucci JS, Delozier T, Quint R, Roussel A, Brune D. Radiation myelopathy of the cervical spinal cord: time, dose and volume factors. Int J Radiat Oncol Biol Phys. 1978 Mar-Apr;4(3-4):239-48.
• Ang KK, Jiang GL, Feng Y, Stephens LC, Tucker SL, Price RE. Extent and kinetics of recovery of occult spinal cord injury. Int J Radiat Oncol Biol Phys. 2001 Jul 15;50(4):1013-20.
• Bilsky MH, Yamada Y, Yenice KM, Lovelock M, Hunt M, Gutin PH, Leibel SA. Intensity-modulated stereotactic radiotherapy of paraspinal tumors: a preliminary report. Neurosurgery. 2004 Apr;54(4):823-30; discussion 830-1.
• Daut RL, Cleeland CS, Flanery RC. Development of the Wisconsin Brief Pain Questionnaire to assess pain in cancer and other diseases. Pain. 1983 Oct;17(2):197-210. doi: 10.1016/0304-3959(83)90143-4.
• Delattre JY, Rosenblum MK, Thaler HT, Mandell L, Shapiro WR, Posner JB. A model of radiation myelopathy in the rat. Pathology, regional capillary permeability changes and treatment with dexamethasone. Brain. 1988 Dec;111 ( Pt 6):1319-36.
• Gerszten PC, Ozhasoglu C, Burton SA, Vogel WJ, Atkins BA, Kalnicki S, Welch WC. CyberKnife frameless stereotactic radiosurgery for spinal lesions: clinical experience in 125 cases. Neurosurgery. 2004 Jul;55(1):89-98; discussion 98-9.
• Glanzmann C, Aberle HG, Horst W. The risk of chronic progressive radiation myelopathy. Strahlentherapie. 1976 Oct;152(4):363-72.
• Nieder C: Recommendation of Human Spinal Cord Re-irradiation Dose Based on Data From 39 Patients. Int J Radiat Oncol Biol Phys 57:373, 2003
• Schultheiss TE, Stephens LC, Jiang GL, Ang KK, Peters LJ. Radiation myelopathy in primates treated with conventional fractionation. Int J Radiat Oncol Biol Phys. 1990 Oct;19(4):935-40.
• Schultheiss TE, Stephens LC, Maor MH. Analysis of the histopathology of radiation myelopathy. Int J Radiat Oncol Biol Phys. 1988 Jan;14(1):27-32. Review.
• Schultheiss TE, Stephens LC. Invited review: permanent radiation myelopathy. Br J Radiol. 1992 Sep;65(777):737-53. Review.

• Responsible Party: John Fiveash, MD, Professor and Vice Chair, University of Alabama at Birmingham Department of Radiation Oncology, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT00573872
• Other Study ID Numbers: F050103003; T0408240012
• First Posted: Dec 14, 2007
• Last Update Posted: Dec 5, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by John Fiveash, MD, Professor and Vice Chair, University of Alabama at Birmingham Department of Radiation Oncology, University of Alabama at Birmingham: Radiosurgery; Phase II; Cancer; Spinal; AVM
• Additional relevant MeSH terms: Arteriovenous Malformations

Study Results

Participant Flow

Arm/Group Title	Spinal Radiosurgery
Arm/Group Description	Patients will be fitted in a custom immobilization device. A CT simulation scan will then be performed to pinpoint intended radiosurgery target producing a computer optimized radiation plan to be confirmed by planning radiation physicist. Patient will then be placed in their immobilization device and aligned with the treatment planning position. Patient then receives radiosurgery. Treatment delivery will be divided into components of 3-5Gy with repeat CT based localization in between each of these components. For all patients, a nominal prescription dose of 24Gy will be entered into the tomotherapy cost function. Once the plan that provides maximal spinal sparing has been generated, the plan will be renormalized to produce no more than 8Gy (prior RT) or 10Gy (no prior RT) to 0.5cc of spinal cord by dividing the single fraction treatment into fractions of 3-5Gy. Radiosurgery: Phase I: 20-25 Gy in 5 fractions Phase II: 9-24 GY in 1 fraction
Period Title: Overall Study
STARTED	43
COMPLETED	32
NOT COMPLETED	11

Baseline Characteristics

Arm/Group Title	Spinal Radiosurgery
Arm/Group Description	Patients will be fitted in a custom immobilization device. A CT simulation scan will then be performed to pinpoint intended radiosurgery target producing a computer optimized radiation plan to be confirmed by planning radiation physicist. Patient will then be placed in their immobilization device and aligned with the treatment planning position. Patient then receives radiosurgery. Treatment delivery will be divided into components of 3-5Gy with repeat CT based localization in between each of these components. For all patients, a nominal prescription dose of 24Gy will be entered into the tomotherapy cost function. Once the plan that provides maximal spinal sparing has been generated, the plan will be renormalized to produce no more than 8Gy (prior RT) or 10Gy (no prior RT) to 0.5cc of spinal cord by dividing the single fraction treatment into fractions of 3-5Gy. Radiosurgery: Phase I: 20-25 Gy in 5 fractions Phase II: 9-24 GY in 1 fraction
Overall Participants	32
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	19 59.4%
>=65 years	13 40.6%
Sex: Female, Male (Count of Participants)
Female	13 40.6%
Male	19 59.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 12.5%
White	28 87.5%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Palliative Response (Pain or Relief of Neurologic Symptoms) From Single Fraction Radiosurgery Delivered With Tomotherapy
Description	Physician's subjective report of palliative pain relief. The maximal benefit patient received (best response) is reported. Scale is pain described as "worse", "stable", "better", or "completely resolved". In the reporting "better" or "completely resolved" indicates response to treatment.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Spinal Radiosurgery
Arm/Group Description	Patients will be fitted in a custom immobilization device. A CT simulation scan will then be performed to pinpoint intended radiosurgery target producing a computer optimized radiation plan to be confirmed by planning radiation physicist. Patient will then be placed in their immobilization device and aligned with the treatment planning position. Patient then receives radiosurgery. Treatment delivery will be divided into components of 3-5Gy with repeat CT based localization in between each of these components. For all patients, a nominal prescription dose of 24Gy will be entered into the tomotherapy cost function. Once the plan that provides maximal spinal sparing has been generated, the plan will be renormalized to produce no more than 8Gy (prior RT) or 10Gy (no prior RT) to 0.5cc of spinal cord by dividing the single fraction treatment into fractions of 3-5Gy. Radiosurgery: Phase I: 20-25 Gy in 5 fractions Phase II: 9-24 GY in 1 fraction
Measure Participants	32
Count of Participants [Participants]	29 90.6%

2. Primary Outcome

Title	Assess the Acute and Late Toxicity of Spinal Radiosurgery
Description	CTCAE version 3. Acute toxicity will be recorded if toxicity occurs early phase or within 3 months, and late toxicity would be any toxicity that follows those 3 months.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Spinal Radiosurgery
Arm/Group Description	Patients will be fitted in a custom immobilization device. A CT simulation scan will then be performed to pinpoint intended radiosurgery target producing a computer optimized radiation plan to be confirmed by planning radiation physicist. Patient will then be placed in their immobilization device and aligned with the treatment planning position. Patient then receives radiosurgery. Treatment delivery will be divided into components of 3-5Gy with repeat CT based localization in between each of these components. For all patients, a nominal prescription dose of 24Gy will be entered into the tomotherapy cost function. Once the plan that provides maximal spinal sparing has been generated, the plan will be renormalized to produce no more than 8Gy (prior RT) or 10Gy (no prior RT) to 0.5cc of spinal cord by dividing the single fraction treatment into fractions of 3-5Gy. Radiosurgery: Phase I: 20-25 Gy in 5 fractions Phase II: 9-24 GY in 1 fraction
Measure Participants	43
Number [events]	4

3. Primary Outcome

Title	Number of Participants With Lack of Tumor Growth at Last Follow-up
Description	Lack of tumor growth by CT or MRI at last follow-up
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Spinal Radiosurgery
Arm/Group Description	Patients will be fitted in a custom immobilization device. A CT simulation scan will then be performed to pinpoint intended radiosurgery target producing a computer optimized radiation plan to be confirmed by planning radiation physicist. Patient will then be placed in their immobilization device and aligned with the treatment planning position. Patient then receives radiosurgery. Treatment delivery will be divided into components of 3-5Gy with repeat CT based localization in between each of these components. For all patients, a nominal prescription dose of 24Gy will be entered into the tomotherapy cost function. Once the plan that provides maximal spinal sparing has been generated, the plan will be renormalized to produce no more than 8Gy (prior RT) or 10Gy (no prior RT) to 0.5cc of spinal cord by dividing the single fraction treatment into fractions of 3-5Gy. Radiosurgery: Phase I: 20-25 Gy in 5 fractions Phase II: 9-24 GY in 1 fraction
Measure Participants	32
Count of Participants [Participants]	21 65.6%

Adverse Events

Arm/Group Title	Spinal Radiosurgery
Arm/Group Description	Patients will be fitted in a custom immobilization device. A CT simulation scan will then be performed to pinpoint intended radiosurgery target producing a computer optimized radiation plan to be confirmed by planning radiation physicist. Patient will then be placed in their immobilization device and aligned with the treatment planning position. Patient then receives radiosurgery. Treatment delivery will be divided into components of 3-5Gy with repeat CT based localization in between each of these components. For all patients, a nominal prescription dose of 24Gy will be entered into the tomotherapy cost function. Once the plan that provides maximal spinal sparing has been generated, the plan will be renormalized to produce no more than 8Gy (prior RT) or 10Gy (no prior RT) to 0.5cc of spinal cord by dividing the single fraction treatment into fractions of 3-5Gy. Radiosurgery: Phase I: 20-25 Gy in 5 fractions Phase II: 9-24 GY in 1 fraction
All Cause Mortality
	Spinal Radiosurgery
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Spinal Radiosurgery
	Affected / at Risk (%)	# Events
Total	1/32 (3.1%)
Nervous system disorders
Worsening neurological symptoms from progressive spinal disease	1/32 (3.1%)	1
Respiratory, thoracic and mediastinal disorders
Hospitalization for Pneumonia	1/32 (3.1%)	1
Other (Not Including Serious) Adverse Events
	Spinal Radiosurgery
	Affected / at Risk (%)	# Events
Total	1/32 (3.1%)
Nervous system disorders
Grade 2 myelopathy	1/32 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.