Soft Tissue SarcomaPhase 2Axi-STSNCT01140737
A Study of Axitinib in Patients With Advanced Angiosarcoma and Other Soft Tissue Sarcomas
A Phase 2 study testing Axitinib in people with Soft Tissue Sarcoma, run by Sheffield Teaching Hospitals NHS Foundation Trust at 13 sites in United Kingdom.
Trial summary
The study objective is to evaluate the therapeutic activity, safety and tolerability of axitinib in patients with advanced/metastatic soft tissue sarcoma who are unsuitable for or have relapsed after standard chemotherapy. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Soft Tissue Sarcoma
- What is being tested?
- Axitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 145 participants
- Where
- 13 sitesUnited Kingdom
- Study dates
- 31 Aug 2010to 8 Jan 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Pathologically confirmed soft tissue sarcoma, including:
- Angiosarcoma, including intermediate and malignant vascular tumours (WHO classification, 2002) and Kaposi's sarcoma.
- Leiomyosarcoma, including uterine, skin or non organ origin.
- Synovial sarcoma.
- Other eligible subtypes of soft tissue sarcoma of Trojani intermediate or high grade, including fibroblastic, fibrohistiocytic, adipocytic, rhabdomyosarcoma, malignant peripheral nerve sheath, and not otherwise specified. See exclusion criteria for ineligible subtypes.
- Locally advanced or metastatic disease incurable by surgery or radiotherapy.
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- Measurable disease according to RECIST criteria.
- Evidence of objective disease progression in the past 6 months, without anticancer treatment since progression.
- Patients ineligible for chemotherapy (eg. through age, clinical condition or patient refusal) or who have received no more than two prior chemotherapy regimens.
- Age >or = 16.
- WHO performance status 0, 1 or 2.
- At least 4 weeks from prior anticancer treatment (surgery, radiotherapy and systemic therapies) and full recovery from all their adverse effects.
- No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be < or = 140 mm Hg, and the baseline diastolic blood pressure readings must be < or = 90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
- Adequate physiological function:
- renal : calculated or measured creatinine clearance > or = 50 ml/min using the Cockcroft-Gault formula (see appendix 5).
- haematological: Absolute Neutrophil Count (ANC) > or = 1.5 x 109/L, platelets > or = 100 x 109/L, International Normalized Ratio (INR) < or = 1.2.
- hepatic: bilirubin within normal range, AST and ALT < or = 3 x upper limit of normal.
- cardiac: Left Ventricular Ejection Fraction (LVEF) measured by Echocardiogram or Multi Gated Acquisition Scan (MUGA) within normal range.
- Urinary protein <2+ by urine dipstick. If dipstick is >2+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours.
- Negative pregnancy test and agrees to comply with contraceptive measures
- Able to swallow oral medication.
Who cannot join
- Ineligible pathological subtypes including:
- Osteosarcoma
- Ewings/Primitive Neuroectodermal Tumour (PNET sarcomas)
- Chondrosarcoma
- Gastrointestinal stromal tumours (GIST)
- Dermatofibrosarcoma protuberans (DFSP)
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- Malignant mesothelioma
- Mixed mesodermal tumours of uterus
- Known central nervous system metastases.
- Age < 16.
- 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).
- Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, voriconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir and lopinavir).
- Previous malignancies (except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or breast) within the past 3 years.
- Heart failure > or = New York Heart Association (NYHA) class II.
- 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).
- Patients with cavitating lung metastases or any metastasis abutting or invading a major pulmonary blood vessel on baseline CT or MRI scan.
- History of bleeding diathesis or coagulopathy within 12 months of study entry
- Any of the following within the 12 months prior to trial 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.
- Therapeutic dose warfarin. Low molecular weight heparin is permitted.
- Regular treatment with antiplatelet medication, including aspirin >325 mg/day or NSAIDs
- History of malabsorption or major gastrointestinal tract resection likely to affect trial drug absorption.
- 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 trial therapy. Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy which should be continued for 4 weeks after the last dose of trial therapy . The definition of effective contraception will be based on the judgment of the Investigator or designee.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United Kingdom13 sites
Aberdeen Royal Infirmary
Aberdeen, Scotland
Bristol Haematology & Oncology Centre
Bristol
Western General Hospital
Edinburgh, Scotland
St. James's Hospital
Leeds
Royal Marsden Hospital
London
Royal Marsden
London
University College London Hospitals
London
Christies
Manchester
Clatterbridge Centre for Oncology
Metropolitan Borough of Wirral
Nottingham City Hospital
Nottingham
Churchill Hospital
Oxford
Penella Woll
Sheffield
Southampton General Hospital
Southampton
About this study
Official title: A Clinicopathological Phase II Study of Axitinib in Patients With Advanced Angiosarcoma and Other Soft Tissue Sarcomas
The study objective is to evaluate the therapeutic activity, safety and tolerability of axitinib in patients with advanced/metastatic soft tissue sarcoma who are unsuitable for or have relapsed after standard chemotherapy. The therapeutic activity will be separately assessed in angiosarcoma, synovial sarcoma, leiomyosarcomas and other sarcomas.
Read the detailed description
Soft tissue sarcomas are a heterogeneous group of rare malignancies that account for 0.72% of new malignancies and 0.65% of malignant deaths. Advanced sarcomas carry a poor prognosis. Angiogenesis is a hallmark of tumour growth, and there is increasing evidence that antiangiogenic drugs, including axitinib, can lead to tumour regression and improve patient survival in a variety of tumours.
Patients with angiosarcoma, synovial sarcoma, leiomyosarcoma and other sarcomas will be separately evaluated.
Patients will take axitinib 5mg tablets by mouth twice daily. This will be continued for 2 years or until disease progression, or development of limiting toxicity. In the event of severe toxicity, axitinib will be stopped until the toxicity has improved. Treatment may be interrupted for a maximum of 2 weeks. Following this, axitinib can be restarted at a lower dose of 3 mg twice daily. If the toxicity has not improved sufficiently, axitinib will be permanently stopped.
Patients will be monitored once weekly for the first month, then at 4 week intervals. Toxicity will be closely monitored. At each clinic visit, patients will have a physical examination and a routine blood test. A Chest x-ray, CT and/or MRI scans will be done before study entry, then every 12 weeks and at the end of treatment. Disease evaluation will be carried out 12 weeks after study entry, then every 12 weeks until disease progression. After disease progression, patients will be followed up every 3 months for survival. Patients will be followed up until death or a minimum follow up period of 1 year.
Patients will be enrolled from hospitals all over the UK.
- Conditions
- Soft Tissue Sarcoma
- Being tested
- Axitinib
- Keywords
- advanced soft tissue sarcoma
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AxitinibDrug
Also called AG-013736
Patients will take axitinib tablets 5 mg by mouth twice daily continuously. There may be one dose reduction to 3mg 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.
| Study group | Role | What they receive |
|---|---|---|
| Axitinib | Experimental | Patients will take axitinib tablets 5 mg by mouth twice daily continuously. There may be one dose reduction to 3mg twice daily. Receives: Drug: Axitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival rate at 12 weeks after starting treatment, defined according to the Response Evaluation Criteria In Solid Tumours(RECIST criteria)
Disease will be assessed by CT or MRI scan 12 weeks after entry to trial and will be compared to disease measured by CT or MRI scan on entry to the trial or within 4 weeks prior to entry. Response at 12 weeks will be measured using RECIST criteria. Progression-free survival rate is measured as the number of patients who are alive and progression-free at 12 weeks divided by the total number of patients who received at least one cycle of treatment
Measured: 12 weeks after trial entry, the final analysis of the primary outcome measure will take place after all patients have been followed for a minimum of 12 weeks
Secondary outcomes (6)
Tumour response rate (using RECIST criteria)
Disease will be assessed at 12 weeks by CT or MRI scan and clinical photographs where indicated, and compared with disease measured at baseline. Response will be measured using RECIST criteria. Tumour response rate is defined as the number of patients who achieved a complete or partial response divided by the total number of patients who received at least one cycle of treatment.
Measured: 12 weeks and final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Progression-free interval
Progression-free interval is defined as the time from trial entry to date when disease progression first observed where progression is defined in terms of RECIST criteria. Patients who die of disease without disease progression being recorded are defined as progression at date of death. Those that die of other causes are censored at date of death and those who are alive with no recorded progression at time of analysis are censored at date last seen alive and progression-free.
Measured: final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Progression-free survival time
Progression-free survival time is defined in the same way as progression-free interval except that all deaths, whatever the cause, are included as events in the analysis.
Measured: final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Overall survival time
Survival time is measured from trial entry to death from any cause or to date last seen alive for those patients who are still alive at the time of analysis.
Measured: final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Change in performance status
Changes in performance status from baseline according to the World Health Organisation (WHO) performance status scale.
Measured: final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Toxicity rate
Adverse events will be graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Toxicity rate is defined as the number of patients experiencing at least one grade 3, 4 or serious adverse reaction divided by the total number of patients who started treatment
Measured: final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2010 (estimated)
- Study start31 Aug 2010
- Primary completion11 Jun 2016
- Study completion8 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Soft Tissue SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 145 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Birmingham, Cancer Research UK, Pfizer
- Responsible party
- Sponsor
- Investigators
- Penella Woll, BMedSci, Principal investigator, Weston Park Hospital, Sheffield, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01140737
- Sponsor's protocol ID
- STH15195
- Other IDs
- 2008-006007-23, 2008
- Acronym
- Axi-STS
- Status last verified
- Feb 2019
- First submitted
- 8 Jun 2010
- Last updated
- 18 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinicopathological Phase II Study of Axitinib in Patients With Advanced Angiosarcoma and Other Soft Tissue Sarcomas
- ClinicalTrials.gov ID
- NCT01140737
- Acronym / sponsor ID
- Axi-STS / STH15195
- Conditions
- Soft Tissue Sarcoma
- Keywords
- advanced soft tissue sarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 145 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University of Birmingham, Cancer Research UK, Pfizer
- Study start
- 31 Aug 2010 (actual)
- Primary completion
- 11 Jun 2016 (actual)
- Study completion
- 8 Jan 2019 (actual)
- First posted
- 9 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study objective is to evaluate the therapeutic activity, safety and tolerability of axitinib in patients with advanced/metastatic soft tissue sarcoma who are unsuitable for or have relapsed after standard chemotherapy. The therapeutic activity will be separately assessed in angiosarcoma, synovial sarcoma, leiomyosarcomas and other sarcomas.
Detailed description
Soft tissue sarcomas are a heterogeneous group of rare malignancies that account for 0.72% of new malignancies and 0.65% of malignant deaths. Advanced sarcomas carry a poor prognosis. Angiogenesis is a hallmark of tumour growth, and there is increasing evidence that antiangiogenic drugs, including axitinib, can lead to tumour regression and improve patient survival in a variety of tumours.
Patients with angiosarcoma, synovial sarcoma, leiomyosarcoma and other sarcomas will be separately evaluated.
Patients will take axitinib 5mg tablets by mouth twice daily. This will be continued for 2 years or until disease progression, or development of limiting toxicity. In the event of severe toxicity, axitinib will be stopped until the toxicity has improved. Treatment may be interrupted for a maximum of 2 weeks. Following this, axitinib can be restarted at a lower dose of 3 mg twice daily. If the toxicity has not improved sufficiently, axitinib will be permanently stopped.
Patients will be monitored once weekly for the first month, then at 4 week intervals. Toxicity will be closely monitored. At each clinic visit, patients will have a physical examination and a routine blood test. A Chest x-ray, CT and/or MRI scans will be done before study entry, then every 12 weeks and at the end of treatment. Disease evaluation will be carried out 12 weeks after study entry, then every 12 weeks until disease progression. After disease progression, patients will be followed up every 3 months for survival. Patients will be followed up until death or a minimum follow up period of 1 year.
Patients will be enrolled from hospitals all over the UK.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Axitinib | Experimental | Drug: AxitinibPatients will take axitinib tablets 5 mg by mouth twice daily continuously. There may be one dose reduction to 3mg twice daily. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (21 listed)
- Pathologically confirmed soft tissue sarcoma, including:
- Locally advanced or metastatic disease incurable by surgery or radiotherapy.
- Measurable disease according to RECIST criteria.
- Evidence of objective disease progression in the past 6 months, without anticancer treatment since progression.
- Patients ineligible for chemotherapy (eg. through age, clinical condition or patient refusal) or who have received no more than two prior chemotherapy regimens.
Key exclusion criteria (22 listed)
- Ineligible pathological subtypes including:
- Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, voriconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir and lopinavir).
- Previous malignancies (except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or breast) within the past 3 years.
- Heart failure > or = New York Heart Association (NYHA) class II.
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AxitinibAlso: AG-013736Patients will take axitinib tablets 5 mg by mouth twice daily continuously. There may be one dose reduction to 3mg 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. | Drug | Axitinib |
Primary outcome
Progression-free survival rate at 12 weeks after starting treatment, defined according to the Response Evaluation Criteria In Solid Tumours(RECIST criteria)
Time frame: 12 weeks after trial entry, the final analysis of the primary outcome measure will take place after all patients have been followed for a minimum of 12 weeks
Disease will be assessed by CT or MRI scan 12 weeks after entry to trial and will be compared to disease measured by CT or MRI scan on entry to the trial or within 4 weeks prior to entry. Response at 12 weeks will be measured using RECIST criteria. Progression-free survival rate is measured as the number of patients who are alive and progression-free at 12 weeks divided by the total number of patients who received at least one cycle of treatment
6 secondary outcomes
Tumour response rate (using RECIST criteria)
Time frame: 12 weeks and final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Progression-free interval
Time frame: final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Progression-free survival time
Time frame: final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Overall survival time
Time frame: final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Change in performance status
Time frame: final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Toxicity rate
Time frame: final analysis of all outcome measures will take place after all patients have been followed up for a minimum of 1 year.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Penella Woll, BMedSci principal investigator
Weston Park Hospital, Sheffield, UK
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Axitinib in people with Soft Tissue Sarcoma, run by Sheffield Teaching Hospitals NHS Foundation Trust at 13 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival rate at 12 weeks after starting treatment, defined according to the Response Evaluation Criteria In Solid Tumours(RECIST criteria) (time frame: 12 weeks after trial entry, the final analysis of the primary outcome measure will take place after all patients have been followed for a minimum of 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2021.