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

NCT ID: NCT01005043

Last Updated: 2020-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-01
• Study Completion Date: 2019-10-31

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.

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.

Conditions

Osteosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

heavy ion radiotherapy (C12)

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: RADIATION

Other Intervention Names

Particle therapy; Radiotherapy with C12; Ion therapy

Eligibility 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

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dietmar Hopp Stiftung

OTHER

Sponsor Role: collaborator

University Hospital Heidelberg

OTHER

Sponsor Role: lead

Responsible Party

Juergen Debus

Prof. Dr. Dr. Jürgen Debus

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juergen Debus, Head of Dep.

Role: PRINCIPAL_INVESTIGATOR

Heidelberger Ionenstrahltherapiezentrum, HIT, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany

Locations

Heidelberger Ionenstrahltherapiezentrum (HIT), Im Neuenheimer Feld 400

Heidelberg, , Germany

Countries

Germany

References

Bielack SS, Wulff B, Delling G, Gobel U, Kotz R, Ritter J, Winkler K. Osteosarcoma of the trunk treated by multimodal therapy: experience of the Cooperative Osteosarcoma study group (COSS). Med Pediatr Oncol. 1995 Jan;24(1):6-12. doi: 10.1002/mpo.2950240103.

Reference Type: BACKGROUND

PMID: 7968796 (View on PubMed)

Kamada T, Tsujii H, Tsuji H, Yanagi T, Mizoe JE, Miyamoto T, Kato H, Yamada S, Morita S, Yoshikawa K, Kandatsu S, Tateishi A; Working Group for the Bone and Soft Tissue Sarcomas. Efficacy and safety of carbon ion radiotherapy in bone and soft tissue sarcomas. J Clin Oncol. 2002 Nov 15;20(22):4466-71. doi: 10.1200/JCO.2002.10.050.

Reference Type: BACKGROUND

PMID: 12431970 (View on PubMed)

Oya N, Kokubo M, Mizowaki T, Shibamoto Y, Nagata Y, Sasai K, Nishimura Y, Tsuboyama T, Toguchida J, Nakamura T, Hiraoka M. Definitive intraoperative very high-dose radiotherapy for localized osteosarcoma in the extremities. Int J Radiat Oncol Biol Phys. 2001 Sep 1;51(1):87-93. doi: 10.1016/s0360-3016(01)01603-0.

Reference Type: BACKGROUND

PMID: 11516856 (View on PubMed)

Zhang H, Yoshikawa K, Tamura K, Tomemori T, Sagou K, Tian M, Kandatsu S, Kamada T, Tsuji H, Suhara T, Suzuki K, Tanada S, Tsujii H. [(11)C]methionine positron emission tomography and survival in patients with bone and soft tissue sarcomas treated by carbon ion radiotherapy. Clin Cancer Res. 2004 Mar 1;10(5):1764-72. doi: 10.1158/1078-0432.ccr-0190-3.

Reference Type: BACKGROUND

PMID: 15014030 (View on PubMed)

Blattmann C, Oertel S, Schulz-Ertner D, Rieken S, Haufe S, Ewerbeck V, Unterberg A, Karapanagiotou-Schenkel I, Combs SE, Nikoghosyan A, Bischof M, Jakel O, Huber P, Kulozik AE, Debus J. Non-randomized therapy trial to determine the safety and efficacy of heavy ion radiotherapy in patients with non-resectable osteosarcoma. BMC Cancer. 2010 Mar 12;10:96. doi: 10.1186/1471-2407-10-96.

Reference Type: DERIVED

PMID: 20226028 (View on PubMed)

Other Identifiers

HITHD-01

Identifier Type: -

Identifier Source: org_study_id