OsteosarcomaPhase 1/2NCT01005043
Therapy Trial to Determine the Safety and Efficacy of Heavy Ion Radiotherapy in Patients With Osteosarcoma
A Phase 1/2 study testing heavy ion radiotherapy (C12) in people with Osteosarcoma, run by University Hospital Heidelberg at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 years and olderHealthy volunteers can take part
- Conditions the study is for
- Osteosarcoma
- What is being tested?
- heavy ion radiotherapy (C12)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteGermany
- Study dates
- 1 Dec 2010to Oct 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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)
Show all 10Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Heidelberger Ionenstrahltherapiezentrum (HIT), Im Neuenheimer Feld 400
Heidelberg, 69120
About this study
Official title: Phase I/II Therapy Trial to Determine the Safety and Efficacy of Heavy Ion Radiotherapy in Patients With Osteosarcoma
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.
Read the 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
- Being tested
- heavy ion radiotherapy (C12)
- Keywords
- non-resectable osteosarcoma, heavy ion radiotherapy, particle therapy, safety, toxicity, survival, radiotherapy
- Medical subject headings
- Osteosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
heavy ion radiotherapy (C12)Radiation
Also called Particle therapy, Radiotherapy with C12, Ion therapy
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.
| Study group | Role | What they receive |
|---|---|---|
| heavy ion radiotherapy | Experimental | 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. Receives: Radiation: heavy ion radiotherapy (C12) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: before, weekly during RT and at follow-up (1, 6 and 19 weeks, 6, 12, 24, 36 48 and 60 months after RT).
Secondary outcomes (1)
tumor response (RECIST criteria), disease free survival, overall survival and description of FDG-PET characteristics before and after RT.
Measured: 6, 12, 24, 36 48 and 60 months after RT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2009 (estimated)
- Study start1 Dec 2010
- Primary completion1 Aug 2018
- Study completionOct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for OsteosarcomaStudies of the same condition, open and under way.
- More trials run by University Hospital HeidelbergThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Heidelberg
- Sponsor type
- University, hospital or other
- Collaborators
- Dietmar Hopp Stiftung
- Responsible party
- Principal investigator, Juergen Debus, Heidelberg University
- Investigators
- Juergen Debus, Head of Dep., Principal investigator, Heidelberger Ionenstrahltherapiezentrum, HIT, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01005043
- Sponsor's protocol ID
- HITHD-01
- Status last verified
- Jan 2020
- First submitted
- 23 Oct 2009
- Last updated
- 10 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 7968796Kamada 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.
PubMed 12431970Oya 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.
PubMed 11516856Zhang 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.
PubMed 15014030Blattmann 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.
PubMed 20226028
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Therapy Trial to Determine the Safety and Efficacy of Heavy Ion Radiotherapy in Patients With Osteosarcoma
- ClinicalTrials.gov ID
- NCT01005043
- Acronym / sponsor ID
- HITHD-01
- Conditions
- Osteosarcoma
- Keywords
- non-resectable osteosarcoma, heavy ion radiotherapy, particle therapy, safety, toxicity, survival, radiotherapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University Hospital HeidelbergUniversity, hospital or other
- Collaborators
- Dietmar Hopp Stiftung
- Study start
- 1 Dec 2010 (actual)
- Primary completion
- 1 Aug 2018 (actual)
- Study completion
- Oct 2019 (actual)
- First posted
- 30 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| heavy ion radiotherapy | Experimental | Radiation: heavy ion radiotherapy (C12)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. |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (7 listed)
- 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%)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| heavy ion radiotherapy (C12)Also: Particle therapy, Radiotherapy with C12, Ion therapyDesired 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. | Radiation | heavy ion radiotherapy |
Primary outcome
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).
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2020.
- Background: PubMed 7968796Bielack 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.
- Background: PubMed 12431970Kamada 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.
- Background: PubMed 11516856Oya 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.
- Background: PubMed 15014030Zhang 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.
- Derived from this study: PubMed 20226028Blattmann 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.
Related trials for Osteosarcoma
RecruitingPhase 1/2
Study of Lurbinectedin Monotherapy in Pediatric and Young Adult Participants With Relapsed/Refractory Ewing Sarcoma
Refractory Ewing Sarcoma, Relapsed Ewing Sarcoma
RecruitingObservational study
Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
Pheochromocytoma, Paraganglioma
RecruitingPhase 2
Iscador® P (Mistletoe) Immunotherapy for Recurrent Resectable Osteogenic Sarcoma
Osteogenic Sarcoma Recurrent
RecruitingPhase 2
The CATSINDO Trial - Clinical and Translational Study in Newly Diagnosed Osteosarcoma
Osteosarcoma in Children, Osteosarcoma in Adolescents and Young Adults
RecruitingPhase 2
Evaluating Efficacy of B7-H3-CAR T Cells Administered at the End of Upfront Map Chemotherapy in Patients With Newly Diagnosed High-Risk Osteosarcoma
Pediatric Osteosarcoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juergen Debus, Head of Dep. principal investigator
Heidelberger Ionenstrahltherapiezentrum, HIT, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing heavy ion radiotherapy (C12) in people with Osteosarcoma, run by University Hospital Heidelberg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01005043, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2020.