Clinical trial NCT00186992: Radiation Therapy to Treat Musculoskeletal Tumors
Official title: Image Guided Radiotherapy for the Treatment of Musculoskeletal Tumors: A Phase II Prospective Evaluation of Radiation-related Treatment Effects
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Sarcoma, Ewing's
Rhabdomyosarcoma
Soft Tissue Sarcoma
Musculoskeletal Tumors
Keywords: Sarcoma
radiation therapy
Other musculoskeletal tumors
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: Lance Armstrong Foundation
First posted: 2005-09-16
Enrollment: 202
Sex: ALL
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Researchers at St. Jude Children's Research Hospital are looking for more effective ways to deliver radiation therapy to pediatric tumors of the bone and soft tissues. The goal of the study is to improve local control of musculoskeletal tumors with image-guided radiation therapy (IGRT) while minimizing radiation related side effects. IGRT uses computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) images to precisely define tumor location and to carefully plan radiation treatment. This approach allows doctors to deliver highly conformal radiation therapy to the tumor while protecting nearby healthy normal tissues.

Detailed description: The study focuses on the following primary Objectives:

* To estimate local control rates with image guided radiation therapy as defined in this study for patients with primary musculoskeletal tumors (MST).

  * Prospectively establish a baseline estimate of local control for patients with MST (Ewing's sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcoma (STS)) treated with image guided radiation therapy.
  * Demonstrate that the increased level of conformality afforded by image guided radiation therapy does not reduce its efficacy relative to previously utilized non-image guided radiation therapy techniques in patients with Ewing's sarcoma family of tumors, resected soft tissue sarcomas, and group III rhabdomyosarcomas.
  * Assess local and regional patterns of failure for patients with MST treated with image guided radiation therapy relative to their targeted volumes.
  * Provide a long term (\>5 year) estimate of local disease control for patients with MST (Ewing's sarcoma family of tumors (ESFT)), rhabdomyosarcoma (RMS), and non-rhabdomyosarcoma soft tissue sarcoma (STS) treated with image guided radiation therapy.

The study focuses on the following secondary objectives:

* Establish a quantitative baseline estimate of radiation dose-related changes in normal tissues using novel objective measures of somatic change, musculoskeletal function, tissue biochemistry and physiology.

  o Investigate the dose and volume relationship for the developing physis and cortical bone using physical measures and imaging evaluations including:
  * Prospectively investigate whether an age based radiotherapeutic threshold of dose and volume that will induce premature physis closure and alter long bone length can be quantitatively identified.
  * Quantitatively explore the impact of radiation on cortical bone thinning and long bone curvature.
  * Relate radiation dose and volume to late (10+ year) alterations in bone integrity.
* Describe the severity and time course of radiation-induced changes in the soft tissues including muscle.

  * Delineate sequential changes in muscular volume, muscle function and organ function (delineated by imaging and measures of physical function) following image guided radiation for specific muscular groups.
  * Correlate the temporal changes in muscular volume and function with changes in vascularity and metabolism defined by imaging studies.

Eligibility criteria: Inclusion Criteria:

* Age less than or equal to 25 years (new enrollments only). No age limit on participants who reconsent or reenroll.
* Musculoskeletal tumor involving the primary site of origin requiring definitive, pre-operative or post-operative irradiation to that primary site.
* No prior therapeutic irradiation at the primary site except for emergent radiation to the primary site lasting 1 week or less (5 treatment days) that can be dosimetrically accounted for in the analysis.
* Negative serum or urine beta-HCG for females of child bearing age.
* Patients will be stratified into 2 groups for evaluation of secondary objective endpoints based on the absence or presence of metastatic disease.
* Patients may enter this study in specific clinical situations often defined by multimodality protocols that include the use of radiation therapy, including irradiation alone or combined with surgery (following surgical resection that may be macroscopically complete or incomplete, with positive or negative histologic margins) and/or chemotherapy (following neoadjuvant chemotherapy or combined with post-irradiation adjuvant chemotherapy).Patients requiring regional nodal irradiation and/or metastatic site irradiation are allowed as long as the primary site requires radiation.Patients with recurrent tumors or second malignant neoplasms are allowed on this study if the current primary tumor site requiring irradiation has not previously been irradiated. The treatment plan detailed in this study will allow most patients to be concurrently enrolled on institutional and COG studies.
* Patients enrolled prior to amendment 4.0, who are still in active participation will be reconsented to the current version of the protocol (5.0).

Primary outcomes:
measure: Cumulative Incidence of Local Failures at 5 Years in Patients With Image Guided Radiation Therapy
timeFrame: 5-years follow-up after completion of therapy.
measure: Cumulative Incidence of Local Failures at 10 Years in Patients With Image Guided Radiation Therapy
timeFrame: 10- years follow-up after completion of therapy
Secondary outcomes:
measure: Changes in Growth Rate and Length of Bone, Bone Density, Development of Muscle (Muscle Function, e.g. Range of Motion), Occurrence of Organ Specific (e.g. Lung, Skin) CTC Measured Toxicities.
timeFrame: Time to local failure (local control) over 5 years follow-up after completion of therapy
measure: Changes in Growth Rate and Length of Bone, Bone Density, Development of Muscle (Muscle Function, e.g. Range of Motion), Occurrence of Organ Specific (e.g. Lung, Skin) CTC Measured Toxicities.
timeFrame: Time to local failure (local control) over 10 years follow-up after completion of therapy
measure: Muscle Function Over Time, PET, DCE-MR, T2* MR Quantitative Parameters.
timeFrame: Change from baseline as well as comparison to non-treated side (when available) during the first 5 years after completion of therapy.
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Matthew Krasin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hua C, Gray JM, Merchant TE, Kun LE, Krasin MJ. Treatment planning and delivery of external beam radiotherapy for pediatric sarcoma: the St. Jude Children's Research Hospital experience. Int J Radiat Oncol Biol Phys. 2008 Apr 1;70(5):1598-606. doi: 10.1016/j.ijrobp.2007.12.013. Epub 2008 Jan 30.
citation: Krasin MJ, Davidoff AM, Xiong X, Wu S, Hua CH, Navid F, Rodriguez-Galindo C, Rao BN, Hoth KA, Neel MD, Merchant TE, Kun LE, Spunt SL. Preliminary results from a prospective study using limited margin radiotherapy in pediatric and young adult patients with high-grade nonrhabdomyosarcoma soft-tissue sarcoma. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):874-8. doi: 10.1016/j.ijrobp.2009.02.074. Epub 2009 Jul 20.
citation: Krasin MJ, Xiong X, Reddick WE, Ogg RJ, Hoffer FA, McCarville B, Kaste SC, Spunt SL, Navid F, Davidoff AM, Zhang L, Kun LE, Merchant TE. A model for quantitative changes in the magnetic resonance parameters of muscle in children after therapeutic irradiation. Magn Reson Imaging. 2006 Dec;24(10):1319-24. doi: 10.1016/j.mri.2006.08.004. Epub 2006 Oct 25.
citation: Hua C, Shukla HI, Merchant TE, Krasin MJ. Estimating differences in volumetric flat bone growth in pediatric patients by radiation treatment method. Int J Radiat Oncol Biol Phys. 2007 Feb 1;67(2):552-8. doi: 10.1016/j.ijrobp.2006.08.069. Epub 2006 Nov 9.
citation: M.J. Krasin; X. Xiong; L. Zhang; W.E. Reddick; T.E. Merchant. A Prospective Study of Quantitative Changes in the Musculature of Children Treated with Radiation Therapy for Sarcomas International journal of radiation oncology, biology, physics(volume 63 issue Pages S443-S444), 2005
citation: Krasin, M J; T.E. Merchant; S.L. Spunt; A.M. Davidoff; F. Navid; S. Wu; X. Xiong; C. Hua; L.E. Kun Early Results of a Prospective Study Delivering Limited Margin Radiotherapy for Pediatric Non-Rhabdo-Soft Tissue Sarcomas (NRSTS) and Aggressive Fibromatoses (AF) International journal of radiation oncology, biology, physics(volume 66 issue 3 Page S112), 2006
citation: Krasin MJ, MD; Xiong X, PhD; Hua C, PhD; Marchese VG, PT, PhD; Cremer L, PT; Zhang L; Spunt SL, MD; Navid F, MD; Merchant TE, DO,PhD. A Model for Changes in Jaw Function in Children Following Therapeutic Irradiation of the Head and Neck presented at The 9th International Conference on Long-term Complications of Treatment of Children and Adolescents for Cancer, 2006
citation: Tinkle CL, Pappo A, Wu J, Mao S, Hua CH, Shulkin BL, McCarville MB, Kaste SC, Davidoff AM, Bahrami A, Green DM, Ness KK, Merchant TE, Spunt SL, Krasin MJ. Efficacy and Safety of Limited-Margin Conformal Radiation Therapy for Pediatric Rhabdomyosarcoma: Long-Term Results of a Phase 2 Study. Int J Radiat Oncol Biol Phys. 2020 May 1;107(1):172-180. doi: 10.1016/j.ijrobp.2020.01.011. Epub 2020 Jan 25.