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 number | NCT01140737 |
| Secondary identifying numbers | STH15195 |
- 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
Contact information
Prof Penella Woll
Scientific
Scientific
Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom
| p.j.woll@sheffield.ac.uk |
Ms Ana Hughes
Scientific
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 |
|---|---|
| a.i.hughes@bham.ac.uk |
Study information
| Study design | Phase II open-label non-randomised multi-centre parallel-group study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Axitinib |
| Primary outcome measure | Proportion of patients progression-free 12 weeks after starting treatment, defined according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. |
| Secondary outcome measures | 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. |
| Overall study start date | 01/07/2009 |
| Completion date | 08/01/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Between 72 and 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
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Weston Park Hospital
Sheffield
S10 2SJ
United Kingdom
S10 2SJ
United Kingdom
Aberdeen Royal Infirmary
Aberdeen
AB25 2ZN
United Kingdom
AB25 2ZN
United Kingdom
Western General Hospital
Edinburgh
EH4 2XU
United Kingdom
EH4 2XU
United Kingdom
Clatterbridge Centre for Oncology
Bebington
CH63 4JY
United Kingdom
CH63 4JY
United Kingdom
Bristol Haematology & Oncology Centre
Bristol
BS2 8ED
United Kingdom
BS2 8ED
United Kingdom
St. James's Hospital
Leeds
LS9 7TF
United Kingdom
LS9 7TF
United Kingdom
Royal Marsden Hospital
London
SW3 6JJ
United Kingdom
SW3 6JJ
United Kingdom
University College London Hospitals
London
NW1 2BU
United Kingdom
NW1 2BU
United Kingdom
Christie Hospital
Manchester
M20 4BX
United Kingdom
M20 4BX
United Kingdom
Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom
NG5 1PB
United Kingdom
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
OX3 7LE
United Kingdom
Ninewells Hospital
Dundee
DD2 1UB
United Kingdom
DD2 1UB
United Kingdom
Singleton Hospital
Swansea
SA2 8QA
United Kingdom
SA2 8QA
United Kingdom
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
SO16 6YD
United Kingdom
Sponsor information
Sheffield Teaching Hospitals NHS Foundation Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Pegasus House
463a Glossop Road
Sheffield
S10 2QD
England
United Kingdom
| Website | http://www.sth.nhs.uk/ |
|---|---|
"ROR" |
https://ror.org/018hjpz25 |
Funders
Funder type
Charity
Cancer Research UK (UK) (ref: C5410/A10910)
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Pfizer (USA) (supplementary funding)
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- Pfizer Inc., Pfizer Consumer Healthcare, Davis, Charles Pfizer & Company, Warner-Lambert, King Pharmaceuticals, Wyeth Pharmaceuticals, Seagen
- Location
- United States of America
Results and Publications
| Intention to publish date | 31/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planning to submit main trial results to a peer reviewed journal by end of Q£ 2020 (updated 05/03/2020, previously: Q2 2018). |
| 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? |
|---|---|---|---|---|---|
| Basic results | version 1.0 | 02/09/2022 | 08/09/2022 | No | No |
| Results article | 08/09/2023 | 11/09/2023 | Yes | No |
Additional files
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.
