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Therapy Trial to Determine the Safety and Efficacy of Heavy Ion Radiotherapy in Patients With Osteosarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01005043
Recruitment Status : Completed
First Posted : October 30, 2009
Last Update Posted : January 10, 2020
Sponsor:
Collaborator:
Dietmar Hopp Stiftung
Information provided by (Responsible Party):
Juergen Debus, Heidelberg University

Brief Summary:
The primary objectives of this trial are the determination of feasibility and toxicity of Heavy Ion Radiotherapy (C12) in patients with non-resectable osteosarcoma. Secondary endpoints are tumor response, disease free survival and overall survival. The aim is to improve outcome for patients with non-resectable osteosarcoma.

Condition or disease Intervention/treatment Phase
Osteosarcoma Radiation: heavy ion radiotherapy (C12) Phase 1 Phase 2

Detailed Description:

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. For effective treatment, local control of the tumor is absolutely critical, because the chances of long term survival are <10% and might effectively approach zero if a complete surgical resection of the tumor is not possible. Up to date there is no curative treatment protocol for patients with non-resectable osteosarcomas, who are excluded from current osteosarcoma trials , e.g. EURAMOS1. Local photon radiotherapy has previously been used in small series and in an uncontrolled, highly individualized fashion, which, however, documented that high dose radiotherapy can, in principle, be used to achieve local control. Generally the radiation dose that is necessary for a curative approach can hardly be achieved with conventional photon radiotherapy in patients with non-resectable tumors that are usually located near radiosensitive critical organs such as the brain, the spine or the pelvis. In these cases Heavy Ion Radiotherapy (HIT) may offer a promising new alternative. Moreover, compared with photons, heavy ion particles provide a higher physical selectivity because of their finite depth coverage in tissue. They achieve a higher relative biological effectiveness. Phase I/II dose escalation studies of HIT in adults with non-resectable bone and soft tissue sarcomas have already shown favorable results.

Methods/Design: This is a monocenter, non-randomized study for patients older than 6 years of age with non-resectable osteosarcoma. Desired target dose is 60-66 Cobalt Gray Equivalent (GyE). Weekly fractionation of 6 x 3 Gy E is used. HIT will be administered exclusively at the Ion Radiotherapy Center in Heidelberg. Furthermore, FDG-PET imaging characteristics of non-resectable osteosarcoma before and after HIT will be investigated prospectively. Systemic disease before and after HIT is targeted by standard chemotherapy protocols and is not part of this trial.

The primary objectives of this trial are the determination of feasibility and toxicity of HIT. Secondary endpoints are tumor response, disease free survival and overall survival. The aim is to improve outcome for patients with non-resectable osteosarcoma.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Therapy Trial to Determine the Safety and Efficacy of Heavy Ion Radiotherapy in Patients With Osteosarcoma
Actual Study Start Date : December 1, 2010
Actual Primary Completion Date : August 1, 2018
Actual Study Completion Date : October 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: heavy ion radiotherapy
Heavy ion radiotherapy of osteosarcoma with 60 to 66 GyE (20-22 days). Before and after radiotherapy, but not during radiotherapy, chemotherapy is recommended to standard therapy protocols like EURAMOS 1 which is not part of this study.
Radiation: heavy ion radiotherapy (C12)

Desired target of Heavy ion radiotherapy is 60 to 66 Cobalt Gray Equivalent (GyE), whenever possible. It is applied through 1 - 3 isocenter treatment portals. Dose distributions are calculated and dose volume histograms (DVH) are generated. A α/β-ratio of 2 is used for biological plan optimization. Fractionation is planned to be equivalent to 6 x 3 GyE / week. Dosage to organs at risk is minimized. Treatment continues for 20 to 22 days or until one of the following criteria applies:

Other illness that prevents further administration of treatment, Patient or legal guardian decides to withdraw from the study, or changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.

Other Names:
  • Particle therapy
  • Radiotherapy with C12
  • Ion therapy




Primary Outcome Measures :
  1. feasibility, toxicity (tox) measured by the CTC Criteria .Unacceptable:grade 4 tox. A rate of acute tox (≤ 3 months during/after RT) > grade 3 of ≤ 5% and a rate of late tox > grade 3 of ≤ 3% will be acceptable. [ Time Frame: before, weekly during RT and at follow-up (1, 6 and 19 weeks, 6, 12, 24, 36 48 and 60 months after RT). ]

Secondary Outcome Measures :
  1. tumor response (RECIST criteria), disease free survival, overall survival and description of FDG-PET characteristics before and after RT. [ Time Frame: 6, 12, 24, 36 48 and 60 months after RT ]


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Histological diagnosis of high grade osteosarcoma with or without metastases
  • Non-resectable tumor of the pelvis, the skull base or the spine, respectively, incomplete or intralesional tumor resection - as confirmed after evaluation by two orthopedic surgeons (respectively neurosurgeons in case of spine tumors): one local surgeon and one referee surgeon of the University of Heidelberg.
  • Age older than 6 years before start of radiotherapy
  • Adequate performance status (Karnofsky >60%)
  • Adequate blood cell production before the start of HIT in patients with pelvic or spine tumors as defined by: total white cell count (WBC) >1,0/nl; neutrophils > 200/µl; platelet count >20/nl
  • No febrile neutropenia (neutrophils < 200/µl)
  • Written informed consent of the patient or the legal guardians

Non-resectable tumor site means primary tumors affecting anatomic areas of the human body where a surgical total resection (R0) of the tumor is not possible for technical reasons, for example osteosarcoma of the pelvis, spine or the skull base. In any other cases, surgical resection is recommended.

Non-resectability has to be confirmed after evaluation by two orthopedic surgeons (respectively neurosurgeons in case of spine tumors): one local surgeon and one referee surgeon of the University of Heidelberg.

In some cases surgery of the tumor might be possible after HIT. Then we recommend surgical resection of residual tumor afterwards.

Exclusion Criteria:

  • Age younger than 6 years
  • Previous radiotherapy of the field that has to be radiated now
  • Implanted metal within the planned radiation field, that leads to significant artefacts within the target volume
  • Patients receiving any other investigational agents during the time of HIT
  • Performance status (Karnofsky) < 60%)
  • Pregnancy
  • No written informed consent of patient or the legal guardians

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01005043


Locations
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Germany
Heidelberger Ionenstrahltherapiezentrum (HIT), Im Neuenheimer Feld 400
Heidelberg, Germany, 69120
Sponsors and Collaborators
University Hospital Heidelberg
Dietmar Hopp Stiftung
Investigators
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Principal Investigator: Juergen Debus, Head of Dep. Heidelberger Ionenstrahltherapiezentrum, HIT, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Juergen Debus, Prof. Dr. Dr. Jürgen Debus, Heidelberg University
ClinicalTrials.gov Identifier: NCT01005043    
Other Study ID Numbers: HITHD-01
First Posted: October 30, 2009    Key Record Dates
Last Update Posted: January 10, 2020
Last Verified: January 2020
Keywords provided by Juergen Debus, Heidelberg University:
non-resectable osteosarcoma
heavy ion radiotherapy
particle therapy
safety
toxicity
survival
radiotherapy
Additional relevant MeSH terms:
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Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma