A clinicopathological phase II study of axitinib in patients with advanced angiosarcoma and other soft tissue sarcomas - Axi-STS Trial, version 1

Phase 1

Active, not recruiting

• Conditions: Soft tissue sarcoma

• Registration Number: EUCTR2008-006007-23-GB
• Lead Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-15
• Last Update Posted: 2020-07-20

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 152

Inclusion Criteria

a)Pathologically confirmed Trojani intermediate or high grade soft tissue sarcoma, including: angiosarcoma, leiomyosarcoma, synovial sarcoma, other eligible subtypes (defined in protocol).
b)Locally advanced or metastatic disease incurable by surgery or radiotherapy.
c)Measurable disease according to RECIST criteria.
d)Evidence of objective disease progression in the past 6 months.
e)Patients ineligible for chemotherapy or who have received no more than 2 prior regimens.
f)Age > or = 16.
g)WHO performance status 0, 1 or 2.
h)At least 4 weeks from prior anticancer treatment or any surgery and full recovery from all AEs.
i)Adequate physiological function:
•renal : calculated or measured creatinine clearance > or = 50 ml/min.
•haematological: ANC > or = 1.5 x 109/L, platelets > or = 100 x 109/L, INR < or = 1.2.
•hepatic: bilirubin within normal range, AST and ALT < or = 3 x upper limit of normal.
•cardiac: LVEF (measured by ECHO or MUGA) within normal range.
j)Negative pregnancy test and agrees to comply with contraceptive measures.
k)Able to swallow oral medication.

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

a)Ineligible pathological subtypes including: osteosarcoma, Ewings/PNET, chondrosarcoma, GIST, mesothelioma (further details in protocol).
b)Known central nervous system metastases.
c) Age <16.
d)Previous malignancies (except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or breast) within the past 3 years.
e)Uncontrolled or poorly controlled hypertension: systolic BP > or = 150 mmHg or diastolic BP > or = 90 mmHg (further defined in protocol). Heart failure > or = NYHA class II.
f)Therapeutic dose warfarin. Low molecular weight heparin is permitted.
g)History of malabsorption or major gastrointestinal tract resection likely to affect study drug absorption.
h)Heart failure > or = NYHA class II.
i)History of hemoptysis > 2.5 ml of blood (1/2 teaspoonful)in any 24-hour period within prior 2 weeks of enrollment
j)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.
k) Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers.
l) Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors.
m) 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. Further details in protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of the study is to evaluate the therapeutic activity, safety and tolerability of axitinib in patients with advanced soft tissue sarcoma which is incurable by surgery or radiotherapy and unsuitable or unresponsive to standard chemotherapy. The therapeutic activity will be separately assessed in the eligible subtypes.;Secondary Objective: Patient blood and tumour samples will be studied to determine the biological factors related to response to axitinib treatment. As axitinib targets the tumour blood supply, we will focus on the study of biomarkers of angiogenesis.;Primary end point(s): Progression-free survival rate at 12 weeks after starting treatment, defined according to RECIST criteria.