None listed
Conditions
Brief summary
Phase 1 and 2 This study looks at the effectiveness and side effects of different dose strengths of the drug sunitinib used in combination with standard pre-operative radiotherapy for soft-tissue sarcoma. Who is it for? You can join this study if you have soft-tissue sarcoma that has been confirmed by microscopic analysis, and is suitable for preventative radiotherapy and surgery and you are aged 16 years or older. Trial details Location: Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, Australia. Participants will receive treatment over seven and a half weeks’ treatment. This involves 14 days of orally administered sunitinib followed by 5 weeks of combination treatment comprising standard pre-operative radiotherapy and oral administered sunitinib, at varying dosage levels. This research is being carried out 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, and to test the safety of the combination of sunitinib and radiotherapy.
Interventions
Seven and a half weeks treatment: 14 days of oral administered sunitinib followed by 5 weeks of combination treatment comprising standard pre-operative radiotherapy and oral administered sunitinib. During the lead-in phase all patients will receive 50mg of Sunitinib (4 tablets of 12.5 mg) per day. During combination treatment patients will receive either 25mg (dose level 0), 37.5mg (dose level 1) or 12.5mg (dose level -1) per day (a maximum of 3 tablets per day). The first 6 patients will receiv
Seven and a half weeks treatment: 14 days of oral administered sunitinib followed by 5 weeks of combination treatment comprising standard pre-operative radiotherapy and oral administered sunitinib. During the lead-in phase all patients will receive 50mg of Sunitinib (4 tablets of 12.5 mg) per day. During combination treatment patients will receive either 25mg (dose level 0), 37.5mg (dose level 1) or 12.5mg (dose level -1) per day (a maximum of 3 tablets per day). The first 6 patients will receive dose level 0. The dose for each subsequent patient cohort will be determined by the number of dose limiting toxicities (DLTs) observed during treatment. If less than 2 DLTs are observed in the first 6 patients on dose level 0, the next 6 patients will be escalated to dose level 1. If there are less than 2 DLTs in the first 6 patients on dose level 1, dose level 1 will be considered the maximum tolerated dose (MTD) and all subsequent patients will receive dose level 1. If there are 2 or more DLTs in the first 6 patients at dose level 1, the dose for all subsequent patients will be reduced to dose level 0, which will be considered the MTD. If there are 2 DLTs in the first 6 patients on dose level 0, a further 6 patients will be treated at this dose level. If there are 2 DLTs in the second 6 patients at dose level 0, the dose will be increased to dose level 1 for the next 6 patients, and will follow the same rules from dose level 1 (as stated above) to find the MTD. If there are 3 DLTs in the second 6 patients (therefore 5 DLTs in 12 patients on this dose), dose level 0 will be considered the MTD and all subsequent patients will receive dose level 0. If there are more than 3 DLTs in the second 6 patients, the dose for the next 6 patients will be reduced to dose level -1 and the rules from dose level -1 (stated below) will be followed. If there are more than 2 DLTs in the first 6 patients on dose level 0, the next 6 patients will be reduced to dose level -1. If less than 2 of the first 6 patients on dose level -1 have DLTs, dose level -1 will be considered the MTD and all subsequent patients will receive dose level -1. If 2 or more patients have DLTs on dose level -1, the trial will be terminated. External beam radiotherapy is given at a dose of 50.4Gy in 28 fractions (5 days per week) for all patients regardless of Sunitinib dose level.
Sponsors
Peter MacCallum Cancer Centre
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Histologically confirmed soft-tissue sarcoma suitable for neoadjuvant radiotherapy and surgery; minimum age 16 years; Eastern Cooperative Oncology Group (ECOG) performance status =1 or less; 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; and 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.
Outcome results
None listed