A phase II trial of Cediranib in the treatment of patients with Alveolar Soft Part Sarcoma
| ISRCTN | ISRCTN63733470 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN63733470 |
| EudraCT/CTIS number | 2010-021163-33 |
| ClinicalTrials.gov number | NCT01337401 |
| Secondary identifying numbers | ICR-CTSU/2010/10027 (Trials Unit) CCR3448 (Sponsor) |
- Submission date
- 08/12/2010
- Registration date
- 07/02/2011
- Last edited
- 24/01/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Contact information
Prof Ian Judson
Scientific
Scientific
Sycamore House (SRMSYC), DF29
Downs Road
Sutton
Surrey
SM2 5PT
United Kingdom
Ms Sarah Kernaghan
Public
Public
Clinical Trials Programme Manager
ICR - Clinical Trials & Statistics Unit (ICR-CTSU)
Division of Clinical Studies
The Institute of Cancer Research
Sir Richard Doll Building
15 Cotswold Road
Belmont
Sutton
SM2 5NG
United Kingdom
| Phone | +44 (0) 20 8722 4152 |
|---|---|
| casps-icrctsu@icr.ac.uk |
Study information
| Study design | Randomised phase II multi-centre double-blind placebo-controlled clinical trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | A randomised phase II multi-centre double-blind placebo-controlled clinical trial of Cediranib in the treatment of patients with Alveolar Soft Part Sarcoma |
| Study acronym | CASPS |
| Study hypothesis | Alveolar soft part sarcoma (ASPS) is rare, with an incidence in the region of 0.5 - 1% of all sarcomas. Given an approximate annual incidence of sarcomas for the UK of 2,500 (excluding advanced gastrointestinal stromal tumour) a reasonable estimate of incidence for ASPS is 15 cases per annum. However, within this number the incidence of metastatic disease is high; patients typically survive for well in excess of 3 years with slowly progressive metastatic disease. There is no standard accepted therapy for this patient group. The only report of clinical benefit concerned a similar agent, sunitinib, also an inhibitor of vascular endothelial growth factor receptor (VEGFR), as well as of other targets. The limited evidence available suggests that cediranib has unprecedented activity in ASPS and as such, this needs to be confirmed. Owing to the indolent nature of the disease in many cases, and hence the difficulty in proving that disease stabilisation is due to treatment, a formal prospective comparative study is required. The randomised design proposed in CASPS represents the best way of proving that the drug is active in this disease. |
| Ethics approval(s) | UK South London Research Ethics Committee (4), 23/01/2011, ref: 10/H0806/118 |
| Condition | Alveolar soft part sarcoma |
| Intervention | Group 1: Cediranib tablets 30 mg oral once daily until week 24 Group 2: Placebo tablets 30 mg oral once daily until week 24 At week 24 all patients unblinded and may continue with open label cediranib until disease progression or study withdrawal for other reason. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Cediranib |
| Primary outcome measure | 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 | Secondary outcomes: 1. Response rate at week 24, best response using RECISTv1.1 and best reduction (%) in tumour size 2. Progression-free survival and percentage alive and progression-free at 12 months (APF12) 3. Overall survival 4. The safety and tolerability profile of cediranib in patients with ASPS Exploratory objectives: 1. To explore the utility and applicability of Choi response criteria8 in ASPS patients treated with cediranib 2. To explore tissue markers of tumour response to cediranib in original archived biopsies, and optional pre- and post-treatment biopsies 3. To evaluate the changes in circulating markers of angiogenesis from blood samples in response to cediranib 4. To evaluate the changes in circulating endothelial cells/endothelial precursor cells in response to cediranib |
| Overall study start date | 11/05/2011 |
| Overall study end date | 15/01/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | 36 |
| Total final enrolment | 48 |
| Participant inclusion criteria | 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 |
| Participant exclusion criteria | 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 Gilberts 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/√RR) 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 as demonstrated by an absolute neutrophil count less than or equal to 1.5 x 10^9/L or platelet count less than or equal to 100 x 10^9/L 2. Serum bilirubin greater than or equal to 1.5 x upper limit of normal (ULN) (unless Gilbert's syndrome) 3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 2.5 x ULN. If liver metastases are present, ALT or AST greater than 5 x ULN. 4. Serum creatinine greater than 1.5 x ULN or a creatinine clearance (calculated or measured) of less than or equal to 50 mL/min 5. Greater than +1 proteinuria unless urinary protein less than 1.5 g in a 24 hour period or protein/creatinine ratio less than 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 greater than 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 greater than 480 msec (using Bazetts correction, for which the formula is: QTc = QT/vRR) or history of familial long QT syndrome 10. Significant recent haemorrhage (greater than 30 ml bleeding/episode in previous 3 months) or haemoptysis (greater than 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. Known hypersensitivity to cediranib or any of its excipients 16. 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 17. Other concomitant anti-cancer therapy (including LHRH agonists) except steroids 18. Recent history of thrombosis 19. 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 |
| Recruitment start date | 11/05/2011 |
| Recruitment end date | 29/07/2016 |
Locations
Countries of recruitment
- Australia
- England
- Spain
- United Kingdom
Study participating centres
Sycamore House (SRMSYC), DF29
Surrey
SM2 5PT
United Kingdom
SM2 5PT
United Kingdom
Royal Marsden Hospital
Fulham Rd
London
SW3 6JJ
United Kingdom
London
SW3 6JJ
United Kingdom
The Christie Hospital
Wilmslow Rd
Manchester
M20 4BX
United Kingdom
Manchester
M20 4BX
United Kingdom
Bristol Haematology and Oncology Centre
Horfield Rd
Bristol
BS2 8ED
United Kingdom
Bristol
BS2 8ED
United Kingdom
University College London Hospital
235 Euston RD
London
NW1 2BU
United Kingdom
London
NW1 2BU
United Kingdom
Royal Victoria Infirmary
Queen Victoria Rd
Newcastle-upon-Tyne
NE1 4LP
United Kingdom
Newcastle-upon-Tyne
NE1 4LP
United Kingdom
Freeman Hospital
Freeman Rd
Newcastle-upon-Tyne
NE7 7DN
United Kingdom
Newcastle-upon-Tyne
NE7 7DN
United Kingdom
Chris O’Brien Lifehouse
119-143 Missenden Rd
Camperdown
Sydney
NSW 2050
Australia
Camperdown
Sydney
NSW 2050
Australia
Princess Alexandra Hospital
199 Ipswich Rd
Woolloongabba
Brisbane
QLD 4102
Australia
Woolloongabba
Brisbane
QLD 4102
Australia
Hospital de la Santa Creu i Sant Pau
Carrer de Sant Quintí 89
Barcelona
08041
Spain
Barcelona
08041
Spain
Hospital Puerta de Hierro
Calle Manuel de Falla 1
Majadahonda
Madrid
28222
Spain
Majadahonda
Madrid
28222
Spain
Hospital Miguel Servet
Paseo Isabel la Católica 1-3
Zaragoza
50009
Spain
Zaragoza
50009
Spain
Sponsor information
The Institute of Cancer Research/Royal Marsden Hospital NHS Foundation Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Glen House (F125), 2.1
125 Old Brompton Road
London
SW7 3RP
England
United Kingdom
| Website | http://www.icr.ac.uk/ |
|---|---|
"ROR" |
https://ror.org/043jzw605 |
Funders
Funder type
Charity
Cancer Research UK (CRUK) (UK) (ref: CRUK/10/021)
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
AstraZeneca (UK) (ref: ISSRECE0036)
Government organisation / For-profit companies (industry)
Government organisation / For-profit companies (industry)
- Alternative name(s)
- AstraZeneca PLC, Pearl Therapeutics
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 15/01/2021 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The main trial results will be published in a peer-reviewed journal. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/07/2019 | 05/06/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Plain English results | 24/01/2025 | 24/01/2025 | No | Yes |
Additional files
Editorial Notes
24/01/2025: Plain English results added.
05/06/2019: Publication reference and total final enrolment added.
07/02/2019: The public contact has been added.
24/01/2019: The following changes have been made:
1. The overall trial end date has been changed from 29/07/2018 to 15/01/2020.
2. France, Germany and Italy have been removed from the countries of recruitment.
3. Royal Marsden Hospital, The Christie Hospital, Bristol Haematology and Oncology Centre, University College London Hospital, Royal Victoria Infirmary, Freeman Hospital, Chris O’Brien Lifehouse, Princess Alexandra Hospital, Hospital de la Santa Creu i Sant Pau, Hospital Puerta de Hierro and Hospital Miguel Servet have been added to the trial participating centres.
4. A publication and dissemination plan has been added.
5. An IPD sharing plan has been added.
6. An intention to publish date has been added.
17/10/2017: The following changes were made to the trial record:
1. The recruitment end date was changed from 31/07/2019 to 29/07/2016.
2. The overall trial end date was changed from 31/07/2019 to 29/07/2018.
17/04/2014: The overall trial end date was changed from 31/12/2013 to 31/07/2019.
06/10/2011: Germany was added to the countries of recruitment and the overall trial start and end dates were updated. The original overall trial start and end dates were 01/02/2011 and 01/02/2014, respectively.
