A Clinicopathological Phase II Study of Axitinib in Patients With Advanced Angiosarcoma and Other Soft Tissue Sarcomas
Overview
- Phase
- Phase 2
- Intervention
- Axitinib
- Conditions
- Soft Tissue Sarcoma
- Sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Enrollment
- 145
- Locations
- 13
- Primary Endpoint
- Progression-free survival rate at 12 weeks after starting treatment, defined according to the Response Evaluation Criteria In Solid Tumours(RECIST criteria)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
The study objective is to evaluate the therapeutic activity, safety and tolerability of axitinib in patients with advanced/metastatic soft tissue sarcoma who are unsuitable for or have relapsed after standard chemotherapy. The therapeutic activity will be separately assessed in angiosarcoma, synovial sarcoma, leiomyosarcomas and other sarcomas.
Detailed Description
Soft tissue sarcomas are a heterogeneous group of rare malignancies that account for 0.72% of new malignancies and 0.65% of malignant deaths. Advanced sarcomas carry a poor prognosis. Angiogenesis is a hallmark of tumour growth, and there is increasing evidence that antiangiogenic drugs, including axitinib, can lead to tumour regression and improve patient survival in a variety of tumours. Patients with angiosarcoma, synovial sarcoma, leiomyosarcoma and other sarcomas will be separately evaluated. Patients will take axitinib 5mg tablets by mouth twice daily. This will be continued for 2 years or until disease progression, or development of limiting toxicity. In the event of severe toxicity, axitinib will be stopped until the toxicity has improved. Treatment may be interrupted for a maximum of 2 weeks. Following this, axitinib can be restarted at a lower dose of 3 mg twice daily. If the toxicity has not improved sufficiently, axitinib will be permanently stopped. Patients will be monitored once weekly for the first month, then at 4 week intervals. Toxicity will be closely monitored. At each clinic visit, patients will have a physical examination and a routine blood test. A Chest x-ray, CT and/or MRI scans will be done before study entry, then every 12 weeks and at the end of treatment. Disease evaluation will be carried out 12 weeks after study entry, then every 12 weeks until disease progression. After disease progression, patients will be followed up every 3 months for survival. Patients will be followed up until death or a minimum follow up period of 1 year. Patients will be enrolled from hospitals all over the UK.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologically confirmed soft tissue sarcoma, including:
- •Angiosarcoma, including intermediate and malignant vascular tumours (WHO classification, 2002) and Kaposi's sarcoma.
- •Leiomyosarcoma, including uterine, skin or non organ origin.
- •Synovial sarcoma.
- •Other eligible subtypes of soft tissue sarcoma of Trojani intermediate or high grade, including fibroblastic, fibrohistiocytic, adipocytic, rhabdomyosarcoma, malignant peripheral nerve sheath, and not otherwise specified. See exclusion criteria for ineligible subtypes.
- •Locally advanced or metastatic disease incurable by surgery or radiotherapy.
- •Measurable disease according to RECIST criteria.
- •Evidence of objective disease progression in the past 6 months, without anticancer treatment since progression.
- •Patients ineligible for chemotherapy (eg. through age, clinical condition or patient refusal) or who have received no more than two prior chemotherapy regimens.
- •Age \>or =
Exclusion Criteria
- •Ineligible pathological subtypes including:
- •Osteosarcoma
- •Ewings/Primitive Neuroectodermal Tumour (PNET sarcomas)
- •Chondrosarcoma
- •Gastrointestinal stromal tumours (GIST)
- •Dermatofibrosarcoma protuberans (DFSP)
- •Malignant mesothelioma
- •Mixed mesodermal tumours of uterus
- •Known central nervous system metastases.
- •Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampicin, and St. John"s Wort).
Arms & Interventions
Axitinib
Patients will take axitinib tablets 5 mg by mouth twice daily continuously. There may be one dose reduction to 3mg twice daily.
Intervention: Axitinib
Outcomes
Primary Outcomes
Progression-free survival rate at 12 weeks after starting treatment, defined according to the Response Evaluation Criteria In Solid Tumours(RECIST criteria)
Time Frame: 12 weeks after trial entry, the final analysis of the primary outcome measure will take place after all patients have been followed for a minimum of 12 weeks
Disease will be assessed by CT or MRI scan 12 weeks after entry to trial and will be compared to disease measured by CT or MRI scan on entry to the trial or within 4 weeks prior to entry. Response at 12 weeks will be measured using RECIST criteria. Progression-free survival rate is measured as the number of patients who are alive and progression-free at 12 weeks divided by the total number of patients who received at least one cycle of treatment
Secondary Outcomes
- Tumour response rate (using RECIST criteria)(12 weeks and final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.)
- Progression-free interval(final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.)
- Change in performance status(final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.)
- Progression-free survival time(final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.)
- Overall survival time(final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.)
- Toxicity rate(final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.)