Standard vs Modified Drug Therapy in Renal Cancer
| ISRCTN | ISRCTN06473203 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN06473203 |
| Secondary identifying numbers | HTA 09/91/21 |
- Submission date
- 15/04/2011
- Registration date
- 15/04/2011
- Last edited
- 10/09/2024
- 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 of protocol
Contact information
Prof Janet Brown
Scientific
Scientific
Unit of Clinical Oncology
University of Sheffield
Sheffield
S10 2SJ
United Kingdom
Study information
| Study design | Randomised controlled open-label multicentre three-stage 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 below to request a patient information sheet |
| Scientific title | A randomised multi-stage, phase II/III trial of standard first-line therapy (sunitinib or pazopanib) comparing temporary cessation with allowing continuation in the treatment of locally advanced and/or metastatic renal cancer |
| Study acronym | STAR |
| Study objectives | Current study hypothesis as of 15/05/2013: The aim of the STAR trial is to evaluate the use of a modified sunitinib or pazopanib schedule compared to the standard sunitinib or pazopanib schedule, in patients with locally advanced and/or metastatic renal cancer. The trial aims to determine whether a modified sunitinib or pazopanib schedule involving a drug-free interval is non-inferior in terms of 2 year overall survival (OS) and quality adjusted life year (QALY) (averaged over trial recruitment and follow-up) compared to sunitinib or pazopanib given according to the standard strategy. Previous study hypothesis until 15/05/2013: The aim of the STAR trial is to evaluate the use of a modified sunitinib schedule compared to the standard sunitinib schedule, in patients with locally advanced and/or metastatic renal cancer. The trial aims to determine whether a modified sunitinib schedule involving a drug-free interval is non-inferior in terms of 2 year overall survival (OS) and quality adjusted life year (QALY) (averaged over trial recruitment and follow-up) compared to a sunitinib given according to the standard strategy. On 15/05/2013 the following changes were made to the trial record: 1. The public title was previously "Standard vs Modified Sunitinib Treatment in Renal Cancer" 2. The scientific title was previously "A randomised multi stage, phase II/III trial of sunitinib. Comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the first-line treatment of locally advanced and/or metastatic renal cancer" On 31/10/2014 the scientific title was changed from 'A randomised multi-stage, phase II/III trial of standard first-line therapy (sunitinib or pazopanib) comparing temporary cessation with allowing continuation, at the time of maximal radiological response, in the treatment of locally advanced and/or metastatic renal cancer' to 'A randomised multi-stage, phase II/III trial of standard first-line therapy (sunitinib or pazopanib) comparing temporary cessation with allowing continuation in the treatment of locally advanced and/or metastatic renal cancer'. More details can be found at http://www.nets.nihr.ac.uk/projects/hta/099121 Protocol can be found at http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0005/54761/PRO-09-91-21.pdf |
| Ethics approval(s) | NRES Committee North West Liverpool Central, 06/06/2011, REC ref: 11/NW/0246 |
| Health condition(s) or problem(s) studied | Locally advanced and/or metastatic clear cell renal cancer |
| Intervention | Current interventions as of 31/10/2014: Sunitinib: one cycle of treatment refers to 50mg (starting dose) od, days 1-28, repeated every 42 days. Pazopanib: one cycle of treatment refers to 800mg (starting dose) od, days 1-42, repeated every 42 days. All patients receive sunitinib or pazopanib and will be randomised to receive either drug according to either a Conventional continuation strategy (CCS) or drug-free interval strategy (DFIS) Control arm: Conventional continuation strategy (CCS) Patients continue sunitinib or pazopanib with regular radiological assessments every 12 weeks until protocol-defined progressive disease (PD) (RECIST), unacceptable cumulative toxicity or patient decision to stop treatment or withdraw from the study. Research arm: Disease-free interval strategy (DFIS) Patients stop treatment after 4 cycles of treatment (i.e. 6 months) and continue 6 weekly active surveillance (clinical assessment) and 12 weekly radiological assessment, with planned recommencement of sunitinib or pazopanib at the time of progressive disease (PD) (RECIST). Assuming further disease control, sunitinib or pazopanib is then continued again for a minimum of 4 cycles. At this point, assuming ongoing disease control, sunitinib or pazopanib can be again temporarily stopped at the discretion of the treating clinician until evidence of PD (RECIST) when again sunitinib or pazopanib is restarted. This DFIS is continued until PD occurs during sunitinib or paozpanib treatment, cumulative toxicity or patient decision to stop treatment or withdraw from the study. Interventions from 15/05/2013 to 31/10/2014: Sunitinib: one cycle of treatment refers to 50mg (starting dose) od, days 1-28, repeated every 42 days. Pazopanib: one cycle of treatment refers to 800mg (starting dose) od, days 1-42, repeated every 42 days. All patients receive sunitinib or pazopanib and will be randomised to receive either drug according to either a Conventional continuation strategy (CCS) or drug-free interval strategy (DFIS) Control arm: Conventional continuation strategy (CCS) Patients continue sunitinib or pazopanib with regular radiological assessments every 12 weeks until protocol-defined progressive disease (PD) (RECIST), unacceptable cumulative toxicity or patient decision to stop treatment or withdraw from the study. Research arm: Disease-free interval strategy (DFIS) Patients stop treatment and continue 6 weekly active surveillance (clinical assessment) and 12 weekly radiological assessment, with planned recommencement of sunitinib or pazopanib at the time of progressive disease (PD) (RECIST). Assuming further disease control, sunitinib or pazopanib is then continued again until the time of maximal radiological response and for a minimum of 4 cycles. At this point, assuming ongoing disease control, sunitinib or pazopanib can be again temporarily stopped until evidence of PD (RECIST) when again sunitinib or pazopanib is restarted. This DFIS is continued until PD occurs during sunitinib or paozpanib treatment, cumulative toxicity or patient decision to stop treatment or withdraw from the study. Interventions from time of registration until 15/05/2013: Sunitinib: one cycle of treatment refers to 50mg (starting dose) od, days 1-28, repeated every 42 days. All patients receive sunitinib and will be randomised to receive it according to either a Conventional continuation strategy (CCS) or drug-free interval strategy (DFIS) Control arm: Conventional continuation strategy (CCS) Patients continue sunitinib with regular radiological assessments every 12 weeks until protocol-defined progressive disease (PD) (RECIST), unacceptable cumulative toxicity or patient decision to stop treatment or withdraw from the study. Research arm: Disease-free interval strategy (DFIS) Patients stop treatment and continue 6 weekly active surveillance (clinical assessment) and 12 weekly radiological assessment, with planned recommencement of sunitinib at the time of progressive disease (PD) (RECIST). Assuming further disease control, sunitinib is then continued again until the time of maximal radiological response and for a minimum of 4 cycles. At this point, assuming ongoing disease control, sunitinib can be again temporarily stopped until evidence of PD (RECIST) when again sunitinib is restarted. This DFIS is continued until PD occurs during sunitinib treatment, cumulative toxicity or patient decision to stop treatment or withdraw from the study. |
| Intervention type | Other |
| Primary outcome measure | 1. Stage A: Recruitment rate/month 2. Stage B: Time to Strategy Failure (TSF) 3. Stage C/Overall: 2 year OS and averaged QALY (over recruitment and follow-up) |
| Secondary outcome measures | 1. Time to strategy failure (TSF) 2. Summative progression free interval (SPFI) 3. Cost effectiveness (health economic endpoints) 4. Toxicity 5. Quality of Life (FACT-G, FSKI-15, EQ-5D and EQ-VAS) 6. Progression free survival (PFS) Ancilliary study: Translational: tissue and imaging |
| Overall study start date | 03/10/2011 |
| Completion date | 31/12/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 210 patients for phase II feasibility, continuing to 1000 patients in phase III trial |
| Total final enrolment | 920 |
| Key inclusion criteria | Current inclusion criteria as of 31/10/2014: 1. Male or female aged ≥ 18 years old 2. Histological confirmation of a component of clear cell renal cell cancer 3. Inoperable loco-regional or metastatic disease 4. No prior systemic therapy for advanced disease (inoperable loco-regional and/or metastatic disease) 4.1 Allowed situation: previous treatment in the SORCE study providing on placebo arm and not active sorafenib arms 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 6. Uni-dimensionally measurable disease (RECIST criteria 7. Full blood count: 7.1 Haemoglobin (Hb) ≥ 9 g/dl 7.2. Absolute Neutrophil Count (ANC) ≥ 1 x 10 9/l 7.3. Platelets ≥ 80 x 10 9/l 8. Renal biochemistry: measured or calculated GFR ≥ 30 ml/min 9. Hepatobiliary function 9.1. Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.5 x ULN 9.2. Bilirubin (BR) ≤ 1.5 x ULN, or in patients with Gilberts syndrome BR ≤ x3 x ULN and direct BR ≤ 35% 10. Provided written informed consent prior to any trial-specific procedures 11. Able and willing to comply with the terms of the protocol including: 11.1. Commencement of sunitinib or pazopanib within 5 (actual not working) days of randomisation 11.2. Temporarily stopping sunitinib or pazopanib if randomised to the DFIS arm 11.3. Capable of oral self-medication 11.4 randomisation within 42 days of the baseline CT scan 11.5. Capable of reporting toxicity and completing quality of life (QoL) and medical resource utilisation (MRU) / Health Economics questionnaires 12. If female and of child-bearing potential, must: 12.1. Have a negative pregnancy test within 72 hours prior to randomisation, and not be breast-feeding 12.2. Agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 30 days after the last dose of sunitinib or pazopanib 13. If male with a partner of child bearing potential, must agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 30 days after the last dose of sunitinib or pazopanib 14. Requirement to start first-line therapy with either sunitinib or pazopanib and decision already made as to which TKI to be used according to local standard practice 15. Allowed situations include: 15.1. Primary renal cancer in-situ or previous nephrectomy 15.2. Previous brain metastases treated with complete surgical resection, Stereotactic Brain Radiation Therapy (SBRT) or gamma knife with no subsequent evidence of progression (patients treated with whole brain radiotherapy are not eligible) 15.3. Previous radiotherapy and/or previous/ongoing bisphosphonates or bone anti-resorptive drugs for the treatment of symptomatic bony metastasis. Care should be taken to follow dental guidelines for the anti-bone resoptive drug. Inclusion criteria from 15/05/2013 to 31/10/2014: 1. Male or female aged ≥ 18 years old 2. Histological confirmation of predominantly clear cell renal cell cancer 3. Inoperable loco-regional or metastatic disease 4. No prior systemic therapy for advanced disease (inoperable loco-regional and/or metastatic disease) 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 6. Uni-dimensionally measurable disease (RECIST criteria, see Appendix 3) 7. Full blood count: 7.1 Haemoglobin (Hb) ≥ 9 g/dl 7.2. Absolute Neutrophil Count (ANC) ≥ 1 x 109/l 7.3. Platelets ≥ 80 x 109/l 8. Renal biochemistry: measured or calculated GFR ≥ 30 ml/min 9. Hepatobiliary function 9.1. Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.5 x ULN 9.2. Bilirubin (BR) ≤ 1.5 x ULN, or or in patients with Gilberts syndrome BR ≤ x3 x ULN and, direct BR ≤ 35% 10. Provided written informed consent prior to any trial-specific procedures 11. Able and willing to comply with the terms of the protocol including: 11.1. Commencement of sunitinib or pazopanib within 3 days of randomisation 11.2. Temporarily stopping sunitinib or pazopanibif randomised to the DFIS arm 11.3. Capable of oral self-medication 11.4. Capable of reporting toxicity and completing quality of life (QoL) and medical resource utilisation (MRU) questionnaires 12. If female and of child-bearing potential, must: 12.1. Have a negative pregnancy test within 72 hours prior to randomisation, and not be breast-feeding 12.2. Agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 6 months after the last dose of sunitinib or pazopanib 13. If male with a partner of child bearing potential, must agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 6 months after the last dose of sunitinib or pazopanib 14. Allowed situations include: 14.1. Primary renal cancer in-situ or previous nephrectomy 14.2. Previous brain metastases treated with complete surgical resection, Stereotactic Brain Radiation Therapy (SBRT) or gamma knife with no subsequent evidence of progression (patients treated with whole brain radiotherapy are not eligible) 14.3. Previous treatment in the SORCE study providing on placebo arm and not active sorafenib arms 14.4. Previous radiotherapy and/or previous/ongoing bisphosphonates or bone anti-resorptive drugs for the treatment of symptomatic bony metastasis Inclusion criteria from time of registration until 15/05/2013: 1. Male or female aged ≥ 18 years old 2. Histological confirmation of predominantly clear cell renal cell cancer 3. Inoperable loco-regional or metastatic disease 4. No prior systemic therapy for advanced disease (inoperable loco-regional and/or metastatic disease) 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 6. Uni-dimensionally measurable disease (RECIST criteria, see Appendix 3) 7. Full blood count: 7.1 Haemoglobin (Hb) ≥ 9 g/dl 7.2. Absolute Neutrophil Count (ANC) ≥ 1 x 109/l 7.3. Platelets ≥ 80 x 109/l 8. Renal biochemistry: measured or calculated GFR ≥ 30 ml/min 9. Hepatobiliary function 9.1. Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.5 x ULN 9.2. Bilirubin (BR) ≤ 1.5 x ULN, or or in patients with Gilberts syndrome BR ≤ x3 x ULN and, direct BR ≤ 35% 10. Provided written informed consent prior to any trial-specific procedures 11. Able and willing to comply with the terms of the protocol including: 11.1. Commencement of sunitinib within 3 days of randomisation 11.2. Temporarily stopping sunitinib if randomised to the DFIS arm 11.3. Capable of oral self-medication 11.4. Capable of reporting toxicity and completing quality of life (QoL) and medical resource utilisation (MRU) questionnaires 12. If female and of child-bearing potential, must: 12.1. Have a negative pregnancy test within 72 hours prior to randomisation, and not be breast-feeding 12.2. Agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 6 months after the last dose of sunitinib 13. If male with a partner of child bearing potential, must agree to use adequate, medically approved, contraceptive precautions (oral or barrier contraceptive under the supervision of a General Practitioner or Family Planning Clinic) during, and for 6 months after the last dose of sunitinib 14. Allowed situations include: 14.1. Primary renal cancer in-situ or previous nephrectomy 14.2. Previous brain metastases treated with complete surgical resection or gamma knife with no subsequent evidence of progression (patients treated with whole brain radiotherapy are not eligible) 14.3. Previous treatment in the SORCE study providing on placebo arm and not active sorafenib arms 14.4. Previous radiotherapy and/or previous/ongoing bisphosphonates or bone anti-resorptive drugs for the treatment of symptomatic bony metastasis |
| Key exclusion criteria | Current exclusion criteria as of 31/10/2014: 1. Pulmonary or mediastinal disease causing obstruction or clinically significant bleeding/haemoptysis 2. Patients with an estimated life expectancy of <6 months 3. Known contraindications to the particular TKI to be used (i.e. sunitinib or pazopanib) 4. Any previous treatment with sunitinib, pazopanib or other tyrosine kinase inhibitor (including in the adjuvant setting) 5. Untreated brain metastases 6. Any concurrent or previous other invasive cancer that could confuse diagnosis or endpoints 6.1. Allowed situations include (but not limited to): non-melanomatous skin cancer or superficial bladder cancer; for all other cases please discuss with Clinical Trials Research Unit (CTRU)) 7. Hypersensitivity to the particular TKI to be used (i.e. sunitinib or pazopanib) 8. Any concomitant medication or substances forming part of local ongoing care known to significantly affect, or have the potential to significantly affect, the activity or pharmacokinetics of the particular TKI to be used (i.e. sunitinib or pazopanib) 9. Poorly controlled hypertension despite maximal medical therapy 10. Any other serious medical or psychiatric condition which in the opinion of the investigator could affect participation in the STAR trial, including gastro-intestinal abnormalities limiting effectiveness of orally administrated drugs, uncontrolled infections, current or recent history of clinically significant cardiovascular disease, significant haemorrhage or gastrointestinal perforation or fistula which, in the opinion of the local investigator, would render the patient unsuitable for standard sunitinib or pazopanib therapy Exclusion criteria from 15/05/2013 to 31/10/2014: 1. Pulmonary or mediastinal disease causing obstruction or bleeding/haemoptysis 2. Patients with an estimated life expectancy of <6 months 3. Known contraindications to sunitinib or pazopanib 4. No previous treatment with sunitinib, pazopanib or other tyrosine kinase inhibitor (including in the adjuvant setting) 5. Untreated brain metastases 6. Any concurrent or previous other invasive cancer that could confuse diagnosis (non-melanomatous skin cancer or superficial bladder cancer acceptable, for all other cases please discuss with Clinical Trials Research Unit (CTRU)) 7. Hypersensitivity to sunitinib or pazopanib 8. Any concomitant medication or substances forming part of local ongoing care known to significantly affect, or have the potential to significantly affect, the activity or pharmacokinetics of sunitinib or pazopanib (see section 10.2 for further information on concomitant medications) 9. Poorly controlled hypertension despite maximal medical therapy 10. Any other serious medical or psychiatric condition which in the opinion of the investigator could affect participation in the STAR trial, including gastro-intestinal abnormalities limiting effectiveness of orally administrated drugs, uncontrolled infections, current or recent history of clinically significant cardiovascular disease, significant haemorrhage or gastrointestinal perforation or fistula which, in the opinion of the local investigator, would render the patient unsuitable for standard sunitinib or pazopanib therapy Exclusion criteria from time of registration until 15/05/2013: 1. Pulmonary or mediastinal disease causing obstruction or bleeding/haemoptysis 2. Patients with an estimated life expectancy of <6 months 3. Known contraindications to sunitinib 4. No previous treatment with sunitinib or other tyrosine kinase inhibitor (including in the adjuvant setting) 5. Untreated brain metastases 6. Any concurrent or previous other invasive cancer that could confuse diagnosis (non-melanomatous skin cancer or superficial bladder cancer acceptable, for all other cases please discuss with Clinical Trials Research Unit (CTRU)) 7. Hypersensitivity to sunitinib 8. Any concomitant medication or substances forming part of local ongoing care known to significantly affect, or have the potential to significantly affect, the activity or pharmacokinetics of sunitinib (see section 10.2 for further information on concomitant medications) 9. Poorly controlled hypertension despite maximal medical therapy 10. Any other serious medical or psychiatric condition which in the opinion of the investigator could affect participation in the STAR trial, including gastro-intestinal abnormalities limiting effectiveness of orally administrated drugs, uncontrolled infections, current or recent history of clinically significant cardiovascular disease which, in the opinion of the local investigator, would render the patient unsuitable for standard sunitinib therapy |
| Date of first enrolment | 03/10/2011 |
| Date of final enrolment | 03/04/2018 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Unit of Clinical Oncology
Sheffield
S10 2SJ
United Kingdom
S10 2SJ
United Kingdom
Sponsor information
University of Leeds (UK)
University/education
University/education
University of Leeds
Leeds
LS2 9JT
England
United Kingdom
"ROR" |
https://ror.org/024mrxd33 |
|---|
Funders
Funder type
Government
NIHR Health Technology Assessment Programme - HTA (UK), Grant Ref: 09/91/21
No information available
Results and Publications
| Intention to publish date | 31/12/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan | De-identified individual participant data datasets generated and/or analysed during the current study will be available upon request from the Clinical Trials Research Unit, University of Leeds (contact CTRU-DataAccess@leeds.ac.uk in the first instance). Data will be made available at the end of the trial, i.e. usually when all primary and secondary endpoints have been met and all key analyses are complete. Data will remain available from then on for as long as CTRU retains the data. CTRU makes data available by a 'controlled access' approach. Data will only be released for legitimate secondary research purposes, where the Chief Investigator, Sponsor and CTRU agree that the proposed use has scientific value and will be carried out to a high standard (in terms of scientific rigour and information governance and security), and that there are resources available to satisfy the request. Data will only be released in line with participants' consent, all applicable laws relating to data protection and confidentiality, and any contractual obligations to which the CTRU is subject. No individual participant data will be released before an appropriate agreement is in place setting out the conditions of release. The agreement will govern data retention, usually stipulating that data recipients must delete their copy of the released data at the end of the planned project. The CTRU encourages a collaborative approach to data sharing, and believe it is best practice for researchers who generated datasets to be involved in subsequent uses of those datasets. Recipients of trial data for secondary research will also receive data dictionaries, copies of key trial documents and any other information required to understand and reuse the released datasets. The conditions of release for aggregate data may differ from those applying to individual participant data. Requests for aggregate data should also be sent to the above email address to discuss and agree suitable requirements for release. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 14/12/2012 | Yes | No | |
| Abstract results | 19/09/2021 | 30/09/2021 | No | No | |
| Results article | 13/02/2023 | 17/02/2023 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Plain English results | 09/02/2024 | No | Yes | ||
| Results article | Temporary treatment cessation compared with continuation of tyrosine kinase inhibitors for adults with renal cancer: the STAR non-inferiority RCT | 01/08/2024 | 10/09/2024 | Yes | No |
Editorial Notes
10/09/2024: Publication reference added.
09/02/2024: CRUK link to plain English results added.
17/02/2023: Publication reference added.
21/10/2022: The following changes were made to the trial record:
1. The participant level data sharing plan was added.
2. The intention to publish date was changed from 31/12/2021 to 31/12/2022.
30/09/2021: The following changes have been made:
1. Abstract added.
2. The final enrolment number has been added from the abstract.
05/10/2020: The following changes have been made:
1. The overall trial end date has been changed from 03/04/2018 to 31/12/2020.
2. The intention to publish date has been added.
22/10/2018: No publications found, verifying study status with principal investigator.
