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A Clinicopathological Phase II Study of Axitinib in Patients With Advanced Angiosarcoma and Other Soft Tissue Sarcomas

Phase 2
16 Years
Open (Enrolling)
Soft Tissue Sarcoma

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Trial Information

A Clinicopathological Phase II Study of Axitinib in Patients With Advanced Angiosarcoma and Other Soft Tissue Sarcomas

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.

Inclusion Criteria:

- 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.

- 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

- 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.

Exclusion Criteria:

- Ineligible pathological subtypes including:

- Osteosarcoma

- Ewings/Primitive Neuroectodermal Tumour (PNET sarcomas)

- Chondrosarcoma

- Gastrointestinal stromal tumours (GIST)

- Dermatofibrosarcoma protuberans (DFSP)

- 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

- 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

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival rate at 12 weeks after starting treatment, defined according to the Response Evaluation Criteria In Solid Tumours(RECIST criteria)

Outcome Description:

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

Outcome 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

Safety Issue:


Principal Investigator

Penella Woll, BMedSci

Investigator Role:

Principal Investigator

Investigator Affiliation:

Weston Park Hospital, Sheffield, UK


United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:




Start Date:

August 2010

Completion Date:

September 2013

Related Keywords:

  • Soft Tissue Sarcoma
  • advanced soft tissue sarcoma
  • Hemangiosarcoma
  • Sarcoma