A phase II trial of Cediranib in the treatment of patients with Alveolar Soft Part Sarcoma
- Conditions
- Alveolar soft part sarcomaCancerSarcoma
- Registration Number
- ISRCTN63733470
- Lead Sponsor
- The Institute of Cancer Research/Royal Marsden Hospital NHS Foundation Trust (UK)
- Brief Summary
2019 results in: https://www.ncbi.nlm.nih.gov/pubmed/31160249 (added 05/06/2019)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 48
Current inclusion criteria as of 11/11/2014:
1. Histologically confirmed diagnosis of ASPS (central confirmation not required at study entry)
2. Age 16 years and older
3. Availability of archived tissue blocks to enable confirmation of t(X;17) translocation
4. ECOG Performance Status of 0-1
5. Life expectancy of >12 weeks
6. Progressive disease as defined by RECIST v1.1 within 6 months prior to randomisation
7. Measurable metastatic disease using RECIST v1.1, i.e. at least one lesion 10 mm in diameter (15 mm in short axis for nodal lesions) assessable by CT (or MRI for brain metastases).
8. Patients with brain metastases are permitted provided disease is controlled with a stable dose of corticosteroid and/or non-enzyme inducing anticonvulsant
9. The capacity to understand the patient information sheet and ability to provide written informed consent
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
11. Able to swallow and retain oral medication
Previous inclusion criteria:
1. Histologically confirmed diagnosis of ASPS (central confirmation not required at study entry)
2. Aged 16 years and older
3. Availability of archived tissue blocks or unstained slides to enable confirmation of t(X;17) translocation
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
5. Life expectancy of greater than 12 weeks
6. Progressive disease within 6 months prior to randomisation
7. Measurable metastatic disease using Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, i.e. at least one lesion 10 mm in diameter (15 mm in short axis for nodal lesions) assessable by spiral computed tomography (CT) (or magnetic resonance imaging [MRI] for brain metastases)
8. Patients with brain metastases are permitted provided disease is controlled with a stable dose of corticosteroid and/or non-enzyme inducing anticonvulsant
9. The capacity to understand the patient information sheet and ability to provide written informed consent
10. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures
11. Able to swallow and retain oral medication
Current exclusion criteria as of 11/11/2014:
1. Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count =1.5 x 109/L or platelet count =100 x 109/L
2. Serum bilirubin = 1.5 x ULN (unless Gilbert?s syndrome)
3. ALT or AST = 2.5 x ULN. If liver metastases are present, ALT or AST > 5 x ULN
4. Serum creatinine > 1.5 x ULN or a creatinine clearance (calculated or measured) of = 50mL/min
5. Greater than +1 proteinuria unless urinary protein < 1.5g in a 24 hr period or protein/creatinine ratio < 1.5.
6. History of significant gastrointestinal impairment, as judged by the Investigator, that would significantly affect the absorption of cediranib.
7. Patients with a history of poorly controlled hypertension with resting blood pressure >150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy.
8. Any evidence of severe or uncontrolled co-morbidities e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease, or active and uncontrolled infection.
9. Evidence of prolonged QTc >480 msec (using Bazetts correction, for which the formula is: QTc = QT/vRR) or history of familial long QT syndrome.
10. Significant recent haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5 mL fresh blood in previous 4 weeks).
11. Major thoracic or abdominal surgery in the 14 days prior to entry into the study, or a surgical incision that is not fully healed.
12. Pregnant or breast-feeding women; women of childbearing potential with a positive pregnancy test prior to receiving study medication; women the intention of pregnancy during study treatment; women of child bearing potential unwilling to have a urine or serum pregnancy test prior to study entry (even if surgically sterilised).
13. Men and women of childbearing potential unwilling to use adequate birth control measures (e.g. abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilisation) for the duration of the study and should continue such precautions for 2 weeks after receiving the last study treatment.
14. History of anticancer (including investigational, non-registered) treatment in the four weeks prior to first dose of cediranib, with the exception of palliative radiotherapy for symptom control.
15. Previous treatment with cediranib.
16. Known hypersensitivity to any excipient of cediranib.
17. History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years, unless the patient has been disease free for 2 years and there is a tissue diagnosis of the primary cancer of interest from a target lesion.
18. Other concomitant anti-cancer therapy (including LHRH agonists) except steroids
19. Recent history of thrombosis
20. Patients with brain metastases if they are symptomatic requiring increasing steroids in the previous six weeks to study entry or those with evidence of recent and/or active bleeding, or those causing uncontrolled seizures.
Previous exclusion criteria:
1. Inadequate bone marrow reserve
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Efficacy of cediranib in the treatment of ASPS by measuring the percentage change in the sum of target marker lesion diameters from randomisation to week 24 (or progression if sooner) compared to treatment with placebo
- Secondary Outcome Measures
Name Time Method <br> Secondary outcomes:<br> 1. Response rate at week 24, best response using RECISTv1.1 and best reduction (%) in tumour size<br> 2. Progression-free survival and percentage alive and progression-free at 12 months (APF12)<br> 3. Overall survival<br> 4. The safety and tolerability profile of cediranib in patients with ASPS<br><br> Exploratory objectives:<br> 1. To explore the utility and applicability of Choi response criteria8 in ASPS patients treated with cediranib<br> 2. To explore tissue markers of tumour response to cediranib in original archived biopsies, and optional pre- and post-treatment biopsies<br> 3. To evaluate the changes in circulating markers of angiogenesis from blood samples in response to cediranib<br> 4. To evaluate the changes in circulating endothelial cells/endothelial precursor cells in response to cediranib<br>