Sunitinib and Radiation in Patients With Resectable Soft-tissue Sarcoma (SUNXRT)

Australasian Sarcoma Study Group

Status and phase

Unknown

Phase 2

Phase 1

Conditions

Soft Tissue Sarcoma

Treatments

Radiation: Radiotherapy

Drug: Sunitinib malate

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00753727

ASSG01

Details and patient eligibility

About

This research is being done with the aim of developing a more effective treatment than standard radiotherapy and surgery alone. Although standard treatment is frequently successful, some patients do not respond well to this treatment. Low oxygen levels in tumours, which may be a particular problem with sarcomas, are thought to be one factor that contributes to failure of radiotherapy. Sunitinib is a new drug that is active against cells with low oxygen levels. The combination of sunitinib and radiotherapy has shown promising results in other cancers. The purpose of this study is to find out whether treatment with a new drug, sunitinib, can increase the effectiveness of radiotherapy at killing cancer cells; to test the safety of the combination of sunitinib and radiotherapy.

Full description

The presence of hypoxia has been documented in soft-tissue sarcomas, where it may contribute to radioresistance. Combinations of radiosensitisers such as ifosfamide and doxorubicin with radiotherapy have demonstrated promise in sarcomas, but with significant toxicity.

The rationale for this study is based on:

the frequency of hypoxia in soft-tissue sarcomas
the importance of radiotherapy in neoadjuvant treatment of soft-tissue sarcomas
targeting hypoxic vasculature with sunitinib
the single agent activity of sunitinib in soft-tissue sarcomas. This study will assess the feasibility and tolerability of the combination of sunitinib with standard preoperative radiotherapy. The surrogate endpoints of tumor necrosis and functional and RECIST imaging response will provide early evidence of response rate. Toxicities will be assessed both during chemoradiation and following surgery. The impact of treatment on the hypoxic component of the tumor will be investigated with F18 azamycin arabinoside PET scans.

Because the combination of sunitinib and radiotherapy has not been studied before, we propose a phase Ib design with dose reductions in the event of excessive toxicity. Sunitinib treatment will precede the commencement of radiotherapy by 2 weeks because there is preclinical evidence that priming the tumor vasculature may increase synergy with radiotherapy, and because sunitinib may have single agent activity in sarcomas, including measurable effects on tumor vasculature. Because it is anticipated that the likelihood of complications attributable to the combination of sunitinib and radiotherapy will be small, the starting dose of sunitinib will be 50mg/day for the two week lead-in period and then 25mg for 5 weeks with concurrent radiotherapy.

Enrollment

26 estimated patients

Sex

All

Ages

16+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histologically confirmed soft-tissue sarcoma suitable for neoadjuvant radiotherapy and surgery
minimum age 16 years
ECOG performance status =1
life expectancy of greater than 6 months
patients must have normal organ and marrow function
no evidence of a bleeding or thrombotic tendency, and no evidence of arterial or venous thrombosis
not pregnant or breastfeeding
the ability to give written informed consent.

Exclusion criteria

Soft-tissue sarcoma located in sites where radiotherapy is associated with significant exposure of abdominal viscera
patients with other invasive malignancies, with the exception of non-melanoma skin cancer, in the last 5 years
patients receiving any other therapeutic investigational agents
patients who are receiving concurrent treatment with any other anti-cancer therapy
evidence of distant metastases
uncontrolled intercurrent illness
patients who are pregnant or breast feeding.