Clinical trial NCT02323295: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malignant Bone Tumors
Keywords: Malignant bone tumors
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-12-23
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Change in Bone Mineral Density (Tb. BMD)
timeFrame: Non-surgical arm: baseline, 3 months Surgical arm: baseline, 9 weeks
Secondary outcomes:
measure: Serum N-Telopeptide (NTX)
timeFrame: Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks, ~7 months, ~10 months
measure: Serum Tartrate-resistant Acid Phosphatase 5b (TRAP5b)
timeFrame: Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks, ~7 months, ~10 months
measure: Serum Osteocalcin (OC)
timeFrame: Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks, ~7 months, ~10 months
measure: Serum Type 1 Procollagen N-terminal (P1NP)
timeFrame: Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks, ~7 months, ~10 months
measure: Serum Phosphate (P)
timeFrame: Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks, ~7 months, ~10 months
measure: Serum 25-hydroxycalciferol Vit D (25-OH VitD)
timeFrame: Non-surgical arm: baseline, 3.5 weeks, 7 weeks, ~5 months, ~8 months Surgical arm: baseline, 5.5 weeks, 18.5 weeks, ~7 months, ~10 months
measure: Mineral Apposition Rate (MAR)
timeFrame: Only surgical arm: The months after biopsies are taken during surgery (surgery is during week 4 and 5). These measurements will be done in batches so timeframe isn't clear.
measure: Bone Formation Rate (BFR/BS)
timeFrame: Only surgical arm: The months after biopsies are taken during surgery (surgery is during week 4 and 5). These measurements will be done in batches so timeframe isn't clear.
measure: Mineralization Lag Time (Mlt)
timeFrame: Only surgical arm: The months after biopsies are taken during surgery (surgery is during week 4 and 5). These measurements will be done in batches so timeframe isn't clear.
measure: Osteoblast Number (N.Ob/BPm)
timeFrame: Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5).
measure: Osteoblast Surface (Ob. S/BS)
timeFrame: Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5).
measure: Osteoclast Number (N.Oc/BPm)
timeFrame: Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5).
measure: Osteoclast Surface (Oc.S/BS)
timeFrame: Only surgical arm: The weeks after biopsies are taken during surgery (surgery is during week 4 and 5).
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Joseph H. Schwab, MD
role: PRINCIPAL_INVESTIGATOR
References: