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A Phase IB/II Study of Sunitinib in Combination With Neoadjuvant Radiation in Patients With Resectable Soft-tissue Sarcoma

Phase 1/Phase 2
16 Years
Open (Enrolling)
Soft Tissue Sarcoma

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Trial Information

A Phase IB/II Study of Sunitinib in Combination With Neoadjuvant Radiation in Patients With Resectable Soft-tissue Sarcoma

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.

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.

Type of Study:


Study Design:

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

Outcome Measure:

To determine the maximum dose of sunitinib at which the combination of sunitinib and radiotherapy pre-operatively is safe and tolerable.

Outcome Time Frame:

Baseline; post-2 weeks sunitinib only administration; post-sunitinib and radiotherapy combination treatment; 12 weeks post-surgery

Safety Issue:


Principal Investigator

David Thomas, MB BS PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Peter MacCallum Cancer Centre, Australia


Australia: Human Research Ethics Committee

Study ID:




Start Date:

September 2008

Completion Date:

March 2016

Related Keywords:

  • Soft Tissue Sarcoma
  • soft tissue
  • Sarcoma
  • Sunitinib
  • neoadjuvant
  • radiotherapy
  • Sarcoma