Boston, Massachusetts 02114


Purpose:

This study is designed to characterize the effects of high energy radiation on bone breakdown, with a specific interest in reducing the rate of sacral fractures. Although radiation is very important in managing tumors, it is related to complications such as bone fractures. In this research study, the investigators are looking to determine changes in blood markers, bone density, and bone structure following radiation and to better understand the reason for these changes.


Study summary:

Participants in the Surgical Arm of the study will be treated according to the schedule outlined in protocol for a combined treatment with surgery and adjuvant high dose radiotherapy. Patients in the non surgical arm of the the study will be treated according to the protocol being treated with radiotherapy alone.


Criteria:

Inclusion Criteria: - All laboratory tests that are a part of the eligibility criteria must be completed within 14 days prior to the date of registration. Diagnostic tests that are a part of the eligibility criteria must be performed within 30 days of the date of registration. Participants must meet the following criteria on screening examination to be eligible to participate in the study: - Study participants must have histologically confirmed primary malignant bone tumor in the sacrum for which surgery and radiation or radiation alone are planned. - Age 18 years or older. In children under the age of 8, tetracycline derivatives have been reported to stain tooth enamel yellow color. These considerations lead us to exclude young persons under the age of 18 from the study. - Participants must have normal organ and marrow function as defined below: - Total bilirubin within normal institutional limits - Aspartaataminotransferase (AST) (SGOT)/ Alanine-aminotransferase (ALT) (SGPT) < 2.5 X institutional upper limit of normal - Creatinine within normal institutional limits or creatinine clearance > 60 mL/min/1.73 m2 for subjects with creatinine levels about institutional normal limit - The effects of tetracyclines and radiation used in computer tomography on the developing human fetus are known to be detrimental. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. - Participants must be able to read and understand English language and have the ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study. - Participants who have had surgery, chemotherapy, or radiotherapy of the sacrum prior to entering the study - History of allergic reactions attributed to compounds of similar chemical or biologic composition to tetracyclines. - Pregnant or nursing - Uncontrolled inter current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements


Study is Available At:


Original ID:

14-208


NCT ID:

NCT02323295


Secondary ID:

C06CA059267


Study Acronym:


Brief Title:

Effect of High Doses of Radiation on Bone Structure and Metabolism


Official Title:

Pilot Study of the Effect of High Doses of Radiation on Bone Metabolism and Structure in Patients Treated With Adjuvant Radiotherapy and Surgery for Sacral Tumors


Overall Status:

Recruiting


Study Phase:

N/A


Genders:

N/A


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Massachusetts General Hospital


Oversight Authority:

United States: Institutional Review Board


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

2


Number of Groups:

0


Total Enrollment:

30


Enrollment Type:

Anticipated


Overall Contact Information

Official Name:Joseph H. Schwab, MD
Principal Investigator
Massachusetts General Hospital
Primary Contact:Joseph Schwab, MD
617-632-2483
jhschwab@partners.org

Study Dates

Start Date:July 2015
Completion Date:July 2019
Completion Type:Anticipated
Primary Completion Date:July 2019
Primary Completion Type:Anticipated
Verification Date:February 2019
Last Changed Date:February 26, 2019
First Received Date:November 21, 2014

Study Outcomes

Outcome Type:Primary Outcome
Measure:Change in Bone mineral density (Tb. BMD)
Time Frame:Non-surgical arm: baseline, 3 months Surgical arm: baseline, 9 weeks
Safety Issues:False
Description:Trabecular bone mineral density will be measured in mg/cm3 using volumetric Quantitative Computed Tomography (QCT) of L1, L2 and the vertebrae adjacent to the tumor.
Outcome Type:Secondary Outcome
Measure:Serum C-Telopeptide (CTX)
Time Frame:Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 wee
Safety Issues:False
Description:Indicator for Bone Formation, units reported in nmol CTX/mmol creatinine
Outcome Type:Secondary Outcome
Measure:Serum Tartrate-resistant acid phosphatase 5b (TRAP5b)
Time Frame:Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 wee
Safety Issues:False
Description:Indicator for Bone Formation, units reported in U/L
Outcome Type:Secondary Outcome
Measure:Serum Osteocalcin (OC)
Time Frame:Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 wee
Safety Issues:False
Description:Indicator for Bone Formation, units reported in ng/mL
Outcome Type:Secondary Outcome
Measure:Serum Type 1 procollagen N-terminal (P1NP)
Time Frame:Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 wee
Safety Issues:False
Description:Indicator for systemic metabolism that can affect bone health, units reported in pg/mL
Outcome Type:Secondary Outcome
Measure:Serum Phosphate (P)
Time Frame:Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 wee
Safety Issues:False
Description:Indicators for systemic metabolism that can affect bone health, units reported in mg/dL
Outcome Type:Secondary Outcome
Measure:Serum 25-hydroxycalciferol Vit D (25-OH VitD)
Time Frame:Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 wee
Safety Issues:False
Description:Indicators for systemic metabolism that can affect bone health, units reported in nmol/L
Outcome Type:Secondary Outcome
Measure:Bone volume fraction (BV/TV)
Time Frame:Only in surgical arm: The week after the surgery, during witch the bone biopsies are taken (the surg
Safety Issues:False
Description:Microscopic computer tomography (micro-CT) will be used and the unit of measure will be the fraction of bone volume / total volume in percentages.
Outcome Type:Secondary Outcome
Measure:Trabecular thickness (Tb.Th.)
Time Frame:Only in surgical arm: The week after the surgery, during witch the bone biopsies are taken (the surg
Safety Issues:False
Description:Microscopic computer tomography (micro-CT) will be used and the unit of measure will be mm.
Outcome Type:Secondary Outcome
Measure:Trabecular number (Tb.N.)
Time Frame:Only in surgical arm: The week after the surgery, during witch the bone biopsies are taken (the surg
Safety Issues:False
Description:Microscopic computer tomography (micro-CT) will be used and the unit of measure will be mm-1
Outcome Type:Secondary Outcome
Measure:Trabecular separation (Tb.Sp.)
Time Frame:Only in surgical arm: The week after the surgery, during witch the bone biopsies are taken (the surg
Safety Issues:False
Description:Microscopic computer tomography (micro-CT) will be used and the unit of measure will be mm.
Outcome Type:Secondary Outcome
Measure:Trabecular bone pattern factor (TBPf)
Time Frame:Only in surgical arm: The week after the surgery, during witch the bone biopsies are taken (the surg
Safety Issues:False
Description:Microscopic computer tomography (micro-CT) will be used and the unit of measure will be mm-1
Outcome Type:Secondary Outcome
Measure:Trabecular Structure model index (SMI)
Time Frame:Only in surgical arm: The week after the surgery, during witch the bone biopsies are taken (the surg
Safety Issues:False
Description:Microscopic computer tomography (micro-CT) will be used. Structure model index indicates the relative prevalence of rods and plates in a 3d structure such as trabecular bone.
Outcome Type:Secondary Outcome
Measure:Trabecular Connectivity density (Conn.D)
Time Frame:Only in surgical arm: The week after the surgery, during witch the bone biopsies are taken (the surg
Safety Issues:False
Description:Microscopic computer tomography (micro-CT) will be used and the unit of measure will be mm-3
Outcome Type:Secondary Outcome
Measure:Bone mineral density distribution (BMDD)
Time Frame:Only in surgical arm: The week after the surgery, during witch the bone biopsies are taken (the surg
Safety Issues:False
Description:Quantitative back scatter electron imaging will be used. BMDD is a frequency distribution of the calcium (Ca) content found in the bone sample.
Outcome Type:Secondary Outcome
Measure:Mineral apposition rate (MAR)
Time Frame:Only surgical arm: The months after biopsies are taken during surgery (surgery is during week 4 and
Safety Issues:False
Description:Tetracycline quadruple labeling method will be used and the unit of measure will be mm/day
Outcome Type:Secondary Outcome
Measure:Bone formation rate (BRF/BS)
Time Frame:Only surgical arm: The months after biopsies are taken during surgery (surgery is during week 4 and
Safety Issues:False
Description:Tetracycline quadruple labeling method will be used and the unit of measure will be mm3/mm2/day
Outcome Type:Secondary Outcome
Measure:Mineralization lag time (Mlt)
Time Frame:Only surgical arm: The months after biopsies are taken during surgery (surgery is during week 4 and
Safety Issues:False
Description:Tetracycline quadruple labeling method will be used and the unit of measure will be days
Outcome Type:Secondary Outcome
Measure:Osteoblast number (N.Ob/BPm)
Time Frame:Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5
Safety Issues:False
Description:Immunohistochemistry staining methods will be used and the unit of measure will be mm-1
Outcome Type:Secondary Outcome
Measure:Osteoblast surface (Ob. S/BS)
Time Frame:Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5
Safety Issues:False
Description:Immunohistochemistry staining methods will be used and the unit of measure will be mm-1
Outcome Type:Secondary Outcome
Measure:Osteoclast number (N.Oc/BPm)
Time Frame:Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5
Safety Issues:False
Description:Immunohistochemistry staining methods will be used and the unit of measure will be mm-1
Outcome Type:Secondary Outcome
Measure:Osteoclast surface (Oc.S/BS)
Time Frame:Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5
Safety Issues:False
Description:Immunohistochemistry staining methods will be used and the unit of measure will be percentages.

Study Interventions

Intervention Type:Radiation
Name:Radiation
Description:For surgical candidates, the standard treatment includes pre-operative radiation of 50.4 Gy, followed by a recovery period of approximately 4 to 5 weeks. After this surgery will take place. After approximately 6 weeks of recovery, to allow the surgical incision to heal, the patient is treated with another 19.8 Gy up to 27 Gy of radiation postoperatively depending on the final margin status (higher for gross residual disease) Non-surgical candidates receive 72 up to 77.14 Gy of radiation dependin
Arm Name:Non Surgical-Radiation Only
Intervention Type:Procedure
Name:Malignant Tumor Surgery
Description:Surgery involves removing the malignant tumor in the sacrum in one piece, preferably with a cuff of normal tissue around the tumor
Arm Name:Malignant Tumor Surgery And Radiation

Study Arms

Study Arm Type:Experimental
Arm Name:Non Surgical-Radiation Only
Description:Non-surgical candidates receive 72 up to 77.l4 Gy of radiation depending on the histology (72 Gy for osteosarcoma and chondrosarcoma and 77.4 Gy for chordoma
Study Arm Type:Experimental
Arm Name:Malignant Tumor Surgery And Radiation
Description:The standard treatment includes pre-operative radiation of 50.4 Gy, followed by a recovery period of approximately 4 to 5 weeks. Surgery involves removing the malignant tumor in the sacrum in one piece, preferably with a cuff of normal tissue around the tumor. After approximately 6 weeks of recovery, the patient is treated with another 19.8 Gy up to 27 Gy of radiation postoperatively depending on the final margin status (higher for gross residual disease). If the wound is not healed or there is

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Massachusetts General Hospital
Agency Class:NIH
Agency Type:Collaborator
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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