Soft Tissue SarcomaPhase 1SunRaSeNCT01498835
Safety Study of Preoperative Sunitinib and Radiation in Soft Tissue Sarcoma
A Phase 1 study testing Sunitinib in people with Soft Tissue Sarcoma, run by Heidelberg University at 2 sites in Germany.
Trial summary
To evaluate the toxicity of sunitinib concurrently given with irradiation for preoperative treatment of locally advanced or recurrent soft tissue sarcoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Soft Tissue Sarcoma
- What is being tested?
- Sunitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesGermany
- Study dates
- Feb 2012to Feb 2015
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- histologically proven soft tissue sarcoma of any histology but GIST, Angiosarcoma, dermatofibrosarcoma protuberans, Ewing Sarcoma or Embryonal Rhabdomyosarcoma
- patients with primary tumors OR with local recurrences who did not receive prior radiation therapy OR with solitary metastatic lesions may be included
- complete resection after neoadjuvant treatment is expected
- age of 18 or older
- ECOG performance score 0 or 1
- normal organ and bone marrow function
- ability to give written informed consent
Who cannot join
- medication with inhibitors or inducers of CYP3A4
- prior therapy with tyrosine kinase inhibitors or conventional chemotherapy within 4 weeks before study inclusion
- history of myocardial infarction, stroke or thromboembolic events
- clinical signs of heart failure (NYHA 3 or 4)
- anticoagulation with Vitamin K antagonists
- acquired or hereditary coagulopathy
Show all 9Show fewer
- uncontrolled hypertension
- uncontrolled intercurrent illness
- women who are pregnant or breastfeeding
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Helios Klinikum Bad Saarow
Bad Saarow, 15526
University Medical Center Mannheim
Mannheim, 68167
About this study
Official title: Phase 1 Trial of Concurrent Sunitinib and Radiation Therapy as Preoperative Treatment for Locally Advanced or Recurrent Soft Tissue Sarcoma.
To evaluate the toxicity of sunitinib concurrently given with irradiation for preoperative treatment of locally advanced or recurrent soft tissue sarcoma.
Read the detailed description
Although the introduction of multimodal treatment of soft tissue sarcoma resulted in great progress in STS treatment, local failure still occurs in 10-20% of STS patients. Therefore further improvement of local and systemic treatment is needed in order to achieve tumor control and limb salvage. The proposed study treatment will combine external beam radiation and orally administered sunitinib.
Sunitinib is a multiple receptor tyrosine kinase (RTK) inhibitor with anti-angiogenic and anti-tumoral properties. For their key role in tumor development, RTKs are regarded as excellent targets for cancer chemotherapy. External beam radiation is widely used as neoadjuvant treatment for locally advanced soft tissue sarcoma.
The concurrent application of anti-angiogenic sunitinib appears reasonable, since STS are highly vascularized tumors and overexpression of VEGFR and other RTKs has been shown for various histologic soft tissue sarcoma subtypes. At first sight, the combination of antiangiogenic treatment and radiation seems to be contradictory, since anti-angiogenic treatment attacks tumor vasculature and radiation effects are decreased by hypoxia. Yet, in animal studies the concurrent application of radiation with tyrosine kinase inhibitors such as sunitinib or other antiangiogenic agents resulted in additive, if not synergistic antitumoral effects. These results can be explained by the superiority of the anti-tumoral activity of antiangiogenic agents over their hypoxia related, radiation weakening effects; or by the hypothesis of vascular normalization. It is well known that tumor vasculature is immature and ineffective in means of blood supply and oxygenation. In preclinical models, antiangiogenic agents balanced pro- and anti-angiogenic effectors which may result in maturation of tumor vasculature with improvement of blood flow and oxygen supply.
The combination of sunitinib as an anti-angiogenic and anti-proliferative agent thus might not only add the therapeutic effects of the RTK-inhibitor and external beam radiation but might additionally lead to a radiosensitizing effect due to tumor vessel normalization. The Purpose of this study is to assess the toxicity of the combined treatment and to gather preliminary data on treatment efficacy.
- Conditions
- Soft Tissue Sarcoma
- Being tested
- Sunitinib
- Keywords
- Soft tissue sarcoma, Radiation therapy, Sunitinib
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SunitinibDrug
Also called Radiation therapy
Patients will receive Sunitinib daily for 2 weeks prior to and then concurrently with irradiation as neoadjuvant treatment. Radiotherapy will be given as intensity modulated radiation therapy with a total dose of 50.4Gy in 28 fractions to each patient (5 1/2 weeks).
Sunitinib will be given in two dose levels. The first dose level will be 25mg Sunitinib per os daily. The second dose level will be 37.5mg sunitinib per os daily. A dose modification schedule according to a 3+3 design will be applied for patient accrual.
| Study group | Role | What they receive |
|---|---|---|
| Combined Sunitinib and irradiation | Experimental | Patients with locally advanced or recurrent soft tissue sarcoma will receive Sunitinib and irradiation as neoadjuvant treatment. Restaging and tumor resection will be performed 6 weeks after completion of sunitinib and irradiation. Receives: Drug: Sunitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the dose limiting toxicity and maximal tolerated dose of sunitinib given concurrently with irradiation as neoadjuvant treatment in soft tissue sarcoma.
Toxicity of the study treatment will be documented according to CTCAE 4.0 during and until 4 weeks after study treatment.
Measured: 12 weeks
Secondary outcomes (1)
To evaluate the response to sunitinib given concurrently with radiation as neoadjuvant treatment in soft tissue sarcoma.
Imaging response will be determined according to RECIST criteria comparing magnetic resonance imaging performed prior to and 6 weeks after completion of study treatment. Pathologic response will be determined evaluating the the fraction of non-viable tumor in the resection specimen.
Measured: 6 weeks after completion of study treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2011 (estimated)
- Study startFeb 2012
- Primary completionNov 2014
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Soft Tissue SarcomaStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Collaborators
- German Research Foundation
- Responsible party
- Principal investigator, Peter Hohenberger, Heidelberg University
- Investigators
- Peter Hohenberger, MD PhD, Principal investigator, Heidelberg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01498835
- Sponsor's protocol ID
- GISG 03
- Other IDs
- 2007-002864-87
- Acronym
- SunRaSe
- Status last verified
- Aug 2017
- First submitted
- 21 Dec 2011
- Last updated
- 28 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jakob J, Simeonova A, Kasper B, Ronellenfitsch U, Rauch G, Wenz F, Hohenberger P. Combined sunitinib and radiation therapy for preoperative treatment of soft tissue sarcoma: results of a phase I trial of the German interdisciplinary sarcoma group (GISG-03). Radiat Oncol. 2016 Jun 3;11:77. doi: 10.1186/s13014-016-0654-2.
PubMed 27255678Jakob J, Rauch G, Wenz F, Hohenberger P. Phase I trial of concurrent sunitinib and radiation therapy as preoperative treatment for soft tissue sarcoma. BMJ Open. 2013 Sep 18;3(9):e003626. doi: 10.1136/bmjopen-2013-003626.
PubMed 24048627
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial of Concurrent Sunitinib and Radiation Therapy as Preoperative Treatment for Locally Advanced or Recurrent Soft Tissue Sarcoma.
- ClinicalTrials.gov ID
- NCT01498835
- Acronym / sponsor ID
- SunRaSe / GISG 03
- Conditions
- Soft Tissue Sarcoma
- Keywords
- Soft tissue sarcoma, Radiation therapy, Sunitinib
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Collaborators
- German Research Foundation
- Study start
- Feb 2012
- Primary completion
- Nov 2014 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 23 Dec 2011 (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.
To evaluate the toxicity of sunitinib concurrently given with irradiation for preoperative treatment of locally advanced or recurrent soft tissue sarcoma.
Detailed description
Although the introduction of multimodal treatment of soft tissue sarcoma resulted in great progress in STS treatment, local failure still occurs in 10-20% of STS patients. Therefore further improvement of local and systemic treatment is needed in order to achieve tumor control and limb salvage. The proposed study treatment will combine external beam radiation and orally administered sunitinib.
Sunitinib is a multiple receptor tyrosine kinase (RTK) inhibitor with anti-angiogenic and anti-tumoral properties. For their key role in tumor development, RTKs are regarded as excellent targets for cancer chemotherapy. External beam radiation is widely used as neoadjuvant treatment for locally advanced soft tissue sarcoma.
The concurrent application of anti-angiogenic sunitinib appears reasonable, since STS are highly vascularized tumors and overexpression of VEGFR and other RTKs has been shown for various histologic soft tissue sarcoma subtypes. At first sight, the combination of antiangiogenic treatment and radiation seems to be contradictory, since anti-angiogenic treatment attacks tumor vasculature and radiation effects are decreased by hypoxia. Yet, in animal studies the concurrent application of radiation with tyrosine kinase inhibitors such as sunitinib or other antiangiogenic agents resulted in additive, if not synergistic antitumoral effects. These results can be explained by the superiority of the anti-tumoral activity of antiangiogenic agents over their hypoxia related, radiation weakening effects; or by the hypothesis of vascular normalization. It is well known that tumor vasculature is immature and ineffective in means of blood supply and oxygenation. In preclinical models, antiangiogenic agents balanced pro- and anti-angiogenic effectors which may result in maturation of tumor vasculature with improvement of blood flow and oxygen supply.
The combination of sunitinib as an anti-angiogenic and anti-proliferative agent thus might not only add the therapeutic effects of the RTK-inhibitor and external beam radiation but might additionally lead to a radiosensitizing effect due to tumor vessel normalization. The Purpose of this study is to assess the toxicity of the combined treatment and to gather preliminary data on treatment efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combined Sunitinib and irradiation | Experimental | Drug: SunitinibPatients with locally advanced or recurrent soft tissue sarcoma will receive Sunitinib and irradiation as neoadjuvant treatment. Restaging and tumor resection will be performed 6 weeks after completion of sunitinib and irradiation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- histologically proven soft tissue sarcoma of any histology but GIST, Angiosarcoma, dermatofibrosarcoma protuberans, Ewing Sarcoma or Embryonal Rhabdomyosarcoma
- patients with primary tumors OR with local recurrences who did not receive prior radiation therapy OR with solitary metastatic lesions may be included
- complete resection after neoadjuvant treatment is expected
- age of 18 or older
- ECOG performance score 0 or 1
Key exclusion criteria (9 listed)
- medication with inhibitors or inducers of CYP3A4
- prior therapy with tyrosine kinase inhibitors or conventional chemotherapy within 4 weeks before study inclusion
- history of myocardial infarction, stroke or thromboembolic events
- clinical signs of heart failure (NYHA 3 or 4)
- anticoagulation with Vitamin K antagonists
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 |
|---|---|---|
| SunitinibAlso: Radiation therapyPatients will receive Sunitinib daily for 2 weeks prior to and then concurrently with irradiation as neoadjuvant treatment. Radiotherapy will be given as intensity modulated radiation therapy with a total dose of 50.4Gy in 28 fractions to each patient (5 1/2 weeks). Sunitinib will be given in two dose levels. The first dose level will be 25mg Sunitinib per os daily. The second dose level will be 37.5mg sunitinib per os daily. A dose modification schedule according to a 3+3 design will be applied for patient accrual. | Drug | Combined Sunitinib and irradiation |
Primary outcome
To evaluate the dose limiting toxicity and maximal tolerated dose of sunitinib given concurrently with irradiation as neoadjuvant treatment in soft tissue sarcoma.
Time frame: 12 weeks
Toxicity of the study treatment will be documented according to CTCAE 4.0 during and until 4 weeks after study treatment.
1 secondary outcome
To evaluate the response to sunitinib given concurrently with radiation as neoadjuvant treatment in soft tissue sarcoma.
Time frame: 6 weeks after completion of study treatment.
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 28 Aug 2017.
- Derived from this study: PubMed 27255678Jakob J, Simeonova A, Kasper B, Ronellenfitsch U, Rauch G, Wenz F, Hohenberger P. Combined sunitinib and radiation therapy for preoperative treatment of soft tissue sarcoma: results of a phase I trial of the German interdisciplinary sarcoma group (GISG-03). Radiat Oncol. 2016 Jun 3;11:77. doi: 10.1186/s13014-016-0654-2.
- Derived from this study: PubMed 24048627Jakob J, Rauch G, Wenz F, Hohenberger P. Phase I trial of concurrent sunitinib and radiation therapy as preoperative treatment for soft tissue sarcoma. BMJ Open. 2013 Sep 18;3(9):e003626. doi: 10.1136/bmjopen-2013-003626.
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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.
Peter Hohenberger, MD PhD principal investigator
Heidelberg University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sunitinib in people with Soft Tissue Sarcoma, run by Heidelberg University at 2 sites 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 7 inclusion and 9 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 28 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 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.
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?
To evaluate the dose limiting toxicity and maximal tolerated dose of sunitinib given concurrently with irradiation as neoadjuvant treatment in soft tissue sarcoma. (time frame: 12 weeks). 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 NCT01498835, which also lists 2 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 28 Aug 2017.