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Phase 1 Trial of Concurrent Sunitinib and Radiation Therapy as Preoperative Treatment for Locally Advanced or Recurrent Soft Tissue Sarcoma.

Phase 1
18 Years
Open (Enrolling)
Soft Tissue Sarcoma

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Trial Information

Phase 1 Trial of Concurrent Sunitinib and Radiation Therapy as Preoperative Treatment for Locally Advanced or Recurrent Soft Tissue Sarcoma.

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.

Inclusion Criteria:

- histologically proven soft tissue sarcoma of any histology but GIST, Angiosarcoma,
dermatofibrosarcoma protuberans, Ewing Sarcoma or Embryonal Rhabdomyosarcoma

- 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

Exclusion Criteria:

- 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

- uncontrolled hypertension

- uncontrolled intercurrent illness

- women who are pregnant or breastfeeding

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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.

Outcome Description:

Toxicity of the study treatment will be documented according to CTCAE 4.0 during and until 4 weeks after study treatment.

Outcome Time Frame:

12 weeks

Safety Issue:


Principal Investigator

Peter Hohenberger, MD PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Heidelberg


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

February 2012

Completion Date:

August 2013

Related Keywords:

  • Soft Tissue Sarcoma
  • Soft tissue sarcoma
  • Radiation therapy
  • Sunitinib
  • Sarcoma