A phase II study of axitinib in patients with advanced angiosarcoma and other soft tissue sarcomas
- Conditions
- Advanced angiosarcoma and other soft tissue sarcomasCancerMalignant neoplasm of other connective and soft tissue
- Registration Number
- ISRCTN60791336
- Lead Sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust (UK)
- Brief Summary
2023 Results article in https://doi.org/10.1038/s41416-023-02416-6 (added 11/09/2023)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 145
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
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 <16 years
4. 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)
5. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors
6. Previous malignancies (except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or breast) within the past 3 years
7. Uncontrolled or poorly controlled hypertension: systolic blood pressure (BP) >=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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method