A phase II study of axitinib in patients with advanced angiosarcoma and other soft tissue sarcomas

Axitinib in patients with advanced angiosarcoma and other soft tissue sarcomas: a phase II open-label parallel-group (non-randomised) study

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN60791336

Enrollment

164

Registered

2009-02-27

Start date

2010-08-31

Completion date

Unknown

Last updated

2023-09-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced angiosarcoma and other soft tissue sarcomas Cancer Malignant neoplasm of other connective and soft tissue

Interventions

All participants will receive the same treatment. However, they will be grouped according to the four pathological subtypes: angiosarcoma, synovial sarcoma, leiomyosarcoma and other (sarcoma, not othe

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1. Pathologically confirmed soft tissue sarcoma, including: 1.1. Angiosarcoma, including intermediate and malignant vascular tumours (World Health Organization [WHO] classification, 2002) and Kaposi's sarcoma 1.2. Leiomyosarcoma, including uterine, skin or non organ origin 1.3. Synovial sarcoma 1.4. Other eligible subtypes of soft tissue sarcoma of Trojani intermediate or high grade, including fibroblastic, fibrohistiocytic, adipocytic, rhabdomyosarcoma, malignant peripheral nerve sheath, and NOS. See exclusion criteria for ineligible subtypes 2. Locally advanced or metastatic disease incurable by surgery or radiotherapy 3. Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) criteria 4. Evidence of objective disease progression in the past 6 months, without anticancer treatment since progression 5. Patients ineligible for chemotherapy (e.g., through age, clinical condition or patient refusal) or who have received no more than two prior chemotherapy regimens 6. Both males and females, age >=16 7. WHO performance status 0, 1 or 2 8. At least 4 weeks from prior anticancer treatment (surgery, radiotherapy and systemic therapies) and full recovery from all their adverse effects 9. Adequate physiological function: 9.1. Renal : calculated or measured creatinine clearance >=50 ml/min 9.2. Haematological: absolute neutrophil count (ANC) >=1.5 x 109/L, platelets >=100 x 109/L, international normalised ratio (INR) <=1.2 9.3. Hepatic: bilirubin within normal range, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=3 x upper limit of normal 9.4. Cardiac: left ventricular ejection fraction (LVEF) (measured by echocardiography [ECHO] or multiple uptake gated acquisition scan [MUGA]) within normal range 10. Negative pregnancy test and agrees to comply with contraceptive measures 11. Able to swallow oral medication

Exclusion criteria

Exclusion criteria: Current exclusion criteria as of 18/10/2011: 1. Ineligible pathological subtypes including: 1.1. Osteosarcoma 1.2. Ewings/primitive neuroectodermal tumour (PNET) sarcomas 1.3. Chondrosarcoma 1.4. Gastrointestinal stromal tumours (GIST) 1.5. Dermatofibrosarcoma protuberans (DFSP) 1.6. Malignant mesothelioma 1.7. Mixed mesodermal tumours of uterus 2. Known central nervous system metastases 3. Age =150 mmHg or diastolic BP >=90 mmHg. Hypertension may be treated prior to study entry, but 3 consecutive readings less than 150/90 must be obtained, at least 24 h apart prior to study entry 8. Heart failure >=NYHA class II 9. History within the previous 6 months of any blood clots in the sputum or streaky haemoptysis that was persistent (> 2 weeks) or recurrent (> 3 episodes). 10. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism 11. Therapeutic dose warfarin. Low molecular weight heparin is permitted. 12. History of malabsorption or major gastrointestinal tract resection likely to affect study drug absorption 13. Pregnancy or breastfeeding. Female patients must be surgically sterile or be postmenopausal, or must agree to use two effective contraception measures during the period of therapy which should be continued for 4 weeks after the last dose of study therapy. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Added 18/10/2011: 14. Regular treatment with antiplatelet medication, including aspirin >325 mg/day or NSAIDs. 15. Patients with cavitating lung metastases or any metatstasis abutting or invading a major pulmonary blood vessel on baseline CT or MRI scan. 16. History of bleeding diathesis or coagulopathy within 12 months of study entry. Previous exclusion criteria: 9. History of hemoptysis >1/2 teaspoon (2.5 ml) of blood in any 24-hour period within prior 2 weeks of enrolment Points 1-8 and 10-13 remained unchanged.

Design outcomes

Primary

Measure	Time frame
Proportion of patients progression-free 12 weeks after starting treatment, defined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria.	—

Secondary

Measure	Time frame
1. Tumour response rate (using RECIST criteria) at end of treatment 2. Time to progression, defined as the interval in whole days between the date of registration into the trial and the earliest date of detection of disease progression 3. Progression-free survival, defined as the interval in whole days between the date of registration into the trial and the earliest of date of detection of disease progression or date of death from any cause. For those patients who do not experience disease progression or die during the course of the trial, progression-free survival times will be censored at the last follow-up date. 4. Overall survival, defined as the interval in whole days between the date of registration into the trial and date of death from any cause; patients who do not die during the course of the trial will be censored at the last follow-up date. 5. Changes in performance status, assessed at screening, weekly during cycle 1, monthly from cycle 2 and at the end of treatment 6. Adverse events, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Report from date of patient enrolment into the study until 30 days after last exposure to the trial treatment. 7. Biomarkers of angiogenesis in blood and tumour biopsy samples. A paraffin-fixed block will be requested from relevant histopathology departments for the pathological and biological studies, for angiosarcomas only, fresh tumour material will be required. If not already available, a core biopsy will be required.	—

Measure

Time frame

1. Tumour response rate (using RECIST criteria) at end of treatment 2. Time to progression, defined as the interval in whole days between the date of registration into the trial and the earliest date of detection of disease progression 3. Progression-free survival, defined as the interval in whole days between the date of registration into the trial and the earliest of date of detection of disease progression or date of death from any cause. For those patients who do not experience disease progression or die during the course of the trial, progression-free survival times will be censored at the last follow-up date. 4. Overall survival, defined as the interval in whole days between the date of registration into the trial and date of death from any cause; patients who do not die during the course of the trial will be censored at the last follow-up date. 5. Changes in performance status, assessed at screening, weekly during cycle 1, monthly from cycle 2 and at the end of treatment 6. Adverse events, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Report from date of patient enrolment into the study until 30 days after last exposure to the trial treatment. 7. Biomarkers of angiogenesis in blood and tumour biopsy samples. A paraffin-fixed block will be requested from relevant histopathology departments for the pathological and biological studies, for angiosarcomas only, fresh tumour material will be required. If not already available, a core biopsy will be required.

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Countries

England, Scotland, United Kingdom, Wales

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Feb 4, 2026