Safety Study of Preoperative Sunitinib and Radiation in Soft Tissue Sarcoma (SunRaSe)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Heidelberg University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
German Research Foundation
Information provided by (Responsible Party):
Peter Hohenberger, University of Heidelberg
ClinicalTrials.gov Identifier:
NCT01498835
First received: December 21, 2011
Last updated: February 10, 2012
Last verified: February 2012
  Purpose

To evaluate the toxicity of sunitinib concurrently given with irradiation for preoperative treatment of locally advanced or recurrent soft tissue sarcoma.


Condition Intervention Phase
Soft Tissue Sarcoma
Drug: Sunitinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Trial of Concurrent Sunitinib and Radiation Therapy as Preoperative Treatment for Locally Advanced or Recurrent Soft Tissue Sarcoma.

Resource links provided by NLM:


Further study details as provided by Heidelberg University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Toxicity of the study treatment will be documented according to CTCAE 4.0 during and until 4 weeks after study treatment.


Secondary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 12
Study Start Date: February 2012
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combined Sunitinib and irradiation
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.
Drug: Sunitinib

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.

Other Names:
  • Sunitinib
  • Radiation therapy

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01498835

Contacts
Contact: Jens Jakob, MD +49 621 383 2447 jens.jakob@umm.de
Contact: Peter Hohenberger, MD PhD +49 621 383 2609 Peter.Hohenberger@umm.de

Locations
Germany
Helios Klinikum Bad Saarow Not yet recruiting
Bad Saarow, Germany, 15526
Contact: Peter Reichardt, MD PhD         
University Medical Center Mannheim Recruiting
Mannheim, Germany, 68167
Contact: Jens Jakob, MD    +49 621 383 2447    jens.jakob@umm.de   
Sponsors and Collaborators
Heidelberg University
German Research Foundation
Investigators
Principal Investigator: Peter Hohenberger, MD PhD Heidelberg University
  More Information

No publications provided

Responsible Party: Peter Hohenberger, MD PhD, University of Heidelberg
ClinicalTrials.gov Identifier: NCT01498835     History of Changes
Other Study ID Numbers: GISG 03, 2007-002864-87
Study First Received: December 21, 2011
Last Updated: February 10, 2012
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Heidelberg University:
Soft tissue sarcoma
Radiation therapy
Sunitinib

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014