Plain English Summary
http://www.cancerhelp.org.uk/trials/a-trial-looking-axitinib-advanced-soft-tissue-sarcoma-Axi-STS
Trial website
Contact information
Type
Scientific
Primary contact
Prof Penella Woll
ORCID ID
Contact details
Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom
-
p.j.woll@sheffield.ac.uk
Type
Scientific
Additional contact
Ms Ana Hughes
ORCID ID
Contact details
Cancer Research UK Clinical Trials Unit (CRCTU)
Institute of Cancer and Genomic Sciences
University of Birmingham
Birmingham
B15 2TT
United Kingdom
+44 (0)121 414 3793
a.i.hughes@bham.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT01140737
Protocol/serial number
STH15195
Study information
Scientific title
Axitinib in patients with advanced angiosarcoma and other soft tissue sarcomas: a phase II open-label parallel-group (non-randomised) study
Acronym
Axi-STS
Study hypothesis
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
West Midlands REC, 15/12/2009
Study design
Phase II open-label non-randomised multi-centre parallel-group study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
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 names
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 trial start date
01/07/2009
Overall trial end date
01/03/2019
Reason abandoned (if study stopped)
Eligibility
Participant 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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Between 72 and 164
Participant 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.
Recruitment start date
31/08/2010
Recruitment end date
01/01/2016
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Weston Park Hospital
Sheffield
S10 2SJ
United Kingdom
Trial participating centre
Aberdeen Royal Infirmary
Aberdeen
AB25 2ZN
United Kingdom
Trial participating centre
Western General Hospital
Edinburgh
EH4 2XU
United Kingdom
Trial participating centre
Clatterbridge Centre for Oncology
Bebington
CH63 4JY
United Kingdom
Trial participating centre
Bristol Haematology & Oncology Centre
Bristol
BS2 8ED
United Kingdom
Trial participating centre
St. James's Hospital
Leeds
LS9 7TF
United Kingdom
Trial participating centre
Royal Marsden Hospital
London
SW3 6JJ
United Kingdom
Trial participating centre
University College London Hospitals
London
NW1 2BU
United Kingdom
Trial participating centre
Christie Hospital
Manchester
M20 4BX
United Kingdom
Trial participating centre
Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom
Trial participating centre
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
Trial participating centre
Ninewells Hospital
Dundee
DD2 1UB
United Kingdom
Trial participating centre
Singleton Hospital
Swansea
SA2 8QA
United Kingdom
Trial participating centre
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
Sponsor information
Organisation
Sheffield Teaching Hospitals NHS Foundation Trust (UK)
Sponsor details
Pegasus House
463a Glossop Road
Sheffield
S10 2QD
United Kingdom
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Charity
Funder name
Cancer Research UK (UK) (ref: C5410/A10910)
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
Pfizer (USA) (supplementary funding)
Alternative name(s)
Pfizer Inc.
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
Results and Publications
Publication and dissemination plan
Planning to submit main trial results to a peer reviewed journal by end of Q2 2018.
IPD sharing statement
The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
31/03/2019
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list