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

ISRCTN	ISRCTN60791336
DOI	https://doi.org/10.1186/ISRCTN60791336
ClinicalTrials.gov (NCT)	NCT01140737
Protocol serial number	STH15195
Sponsor	Sheffield Teaching Hospitals NHS Foundation Trust (UK)
Funders	Cancer Research UK (UK) (ref: C5410/A10910), Pfizer (USA) (supplementary funding)

Submission date: 20/01/2009
Registration date: 27/02/2009
Last edited: 11/09/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-axitinib-advanced-soft-tissue-sarcoma-Axi-STS

Contact information

Prof Penella Woll
Scientific

Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom

Email	p.j.woll@sheffield.ac.uk

Ms Ana Hughes
Scientific

Cancer Research UK Clinical Trials Unit (CRCTU)
Institute of Cancer and Genomic Sciences
University of Birmingham
Birmingham
B15 2TT
United Kingdom

Phone	+44 (0)121 414 3793
Email	a.i.hughes@bham.ac.uk

Study information

Primary study design	Interventional
Study design	Phase II open-label non-randomised multi-centre parallel-group study
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	Axitinib in patients with advanced angiosarcoma and other soft tissue sarcomas: a phase II open-label parallel-group (non-randomised) study
Study acronym	Axi-STS
Study objectives	The study objective is to evaluate the therapeutic activity, safety and tolerability of axitinib in patients with advanced/metastatic soft tissue sarcoma who have relapsed after standard chemotherapy. The therapeutic activity will be separately assessed in angiosarcoma, synovial sarcoma, leiomyosarcomas and other sarcomas.
Ethics approval(s)	West Midlands REC, 15/12/2009
Health condition(s) or problem(s) studied	Advanced angiosarcoma and other soft tissue sarcomas
Intervention	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 otherwise specified [NOS]), and each group (stratum) will be analysed separately (parallel-group analysis). Patients will take axitinib tablets 5 mg by mouth twice daily continuously. There may be one dose reduction to 3 mg twice daily. A four-week dosing period will be considered as 1 cycle of treatment. Axitinib treatment will be continued until disease progression, or the development of limiting toxicity. Disease evaluation will be carried out 12 weeks after study entry (even if the study treatment has already been discontinued) then every 12 weeks until disease progression. After disease progression, patients should be followed up every 3 months for survival. Patients will be followed-up until death or the end of the trial. It is expected to complete accrual in 2 years and the study in 3 years.
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Axitinib
Primary outcome measure(s)	Proportion of patients progression-free 12 weeks after starting treatment, defined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Key secondary outcome measure(s)	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.
Completion date	08/01/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	164
Total final enrolment	145
Key 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
Key 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 <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.
Date of first enrolment	31/08/2010
Date of final enrolment	01/01/2016

Locations

Countries of recruitment

United Kingdom
England
Scotland
Wales

Study participating centres

Weston Park Hospital

Sheffield
S10 2SJ
United Kingdom

Aberdeen Royal Infirmary

Aberdeen
AB25 2ZN
United Kingdom

Western General Hospital

Edinburgh
EH4 2XU
United Kingdom

Clatterbridge Centre for Oncology

Bebington
CH63 4JY
United Kingdom

Bristol Haematology & Oncology Centre

Bristol
BS2 8ED
United Kingdom

St. James's Hospital

Leeds
LS9 7TF
United Kingdom

Royal Marsden Hospital

London
SW3 6JJ
United Kingdom

University College London Hospitals

London
NW1 2BU
United Kingdom

Christie Hospital

Manchester
M20 4BX
United Kingdom

Nottingham City Hospital

Nottingham
NG5 1PB
United Kingdom

Churchill Hospital

Oxford
OX3 7LE
United Kingdom

Ninewells Hospital

Dundee
DD2 1UB
United Kingdom

Singleton Hospital

Swansea
SA2 8QA
United Kingdom

Southampton General Hospital

Southampton
SO16 6YD
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The current data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article		08/09/2023	11/09/2023	Yes	No
Basic results	version 1.0	02/09/2022	08/09/2022	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN60791336_BasicResults_V1.0_02Sep22.pdf: Basic results

Editorial Notes

11/09/2023: Publication reference added.
17/10/2022: Cancer Research UK plain English summary link added to plain English summary field.
08/09/2022: Basic results uploaded.
23/06/2022: The intention to publish date was changed from 30/06/2022 to 31/12/2022.
11/01/2022: The intention to publish date was changed from 31/12/2021 to 30/06/2022.
16/02/2021: The following changes were made to the trial record:
1. The overall trial end date was changed from 01/03/2019 to 08/01/2019.
2. The intention to publish date was changed from 31/08/2020 to 31/12/2021.
3. Total final enrolment added.
05/03/2020: The following changes were made to the trial record:
1. The publication and dissemination plan was updated.
2. The intention to publish date was changed from 31/03/2019 to 31/08/2020.
19/06/2019: No publications found. Verifying results with principal investigator.
22/10/2018: The intention to publish date has been changed from 30/03/2018 to 31/03/2019
10/01/2018: The overall trial end date was changed from 01/12/2017 to 01/03/2019. The intention to publish date was changed from 30/06/2017 to 30/03/2018.
02/06/2017: The overall trial end date was changed from 30/06/2016 to 01/12/2017.
24/02/2011: The overall trial end date was changed from 01/07/2011 to 31/08/2012.