PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma
Abstract Background The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk meta...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2019-11-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12885-019-6273-1 |
| _version_ | 1831723595912445952 |
|---|---|
| author | Hannah L. Buckley Fiona J. Collinson Gemma Ainsworth Heather Poad Louise Flanagan Eszter Katona Helen C. Howard Geraldine Murden Rosamonde E. Banks Joanne Brown Galina Velikova Tom Waddell Kate Fife Paul D. Nathan James Larkin Thomas Powles Sarah R. Brown Naveen S. Vasudev |
| author_facet | Hannah L. Buckley Fiona J. Collinson Gemma Ainsworth Heather Poad Louise Flanagan Eszter Katona Helen C. Howard Geraldine Murden Rosamonde E. Banks Joanne Brown Galina Velikova Tom Waddell Kate Fife Paul D. Nathan James Larkin Thomas Powles Sarah R. Brown Naveen S. Vasudev |
| author_sort | Hannah L. Buckley |
| collection | DOAJ |
| description | Abstract Background The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC) based on recent phase III data. Combining ipilimumab with nivolumab increases rates of grade 3 and 4 toxicity compared with nivolumab alone, and the optimal scheduling of these agents when used together remains unknown. The aim of the PRISM study is to assess whether less frequent dosing of ipilimumab (12-weekly versus 3-weekly), in combination with nivolumab, is associated with a favourable toxicity profile without adversely impacting efficacy. Methods The PRISM trial is a UK-based, open label, multi-centre, phase II, randomised controlled trial. The trial population consists of patients with untreated locally advanced or metastatic clear cell RCC, and aims to recruit 189 participants. Participants will be randomised on a 2:1 basis in favour of a modified schedule of 4 doses of 12-weekly ipilimumab versus a standard schedule of 4 doses of 3-weekly ipilimumab, both in combination with standard nivolumab. The proportion of participants experiencing a grade 3 or 4 adverse reaction within 12 months forms the primary endpoint of the study, but with 12-month progression free survival a key secondary endpoint. The incidence of all adverse events, discontinuation rates, overall response rate, duration of response, overall survival rates and health related quality of life will also be analysed as secondary endpoints. In addition, the potential of circulating and tissue-based biomarkers as predictors of therapy response will be explored. Discussion The combination of nivolumab with ipilimumab is active in patients with mRCC. Modifying the frequency of ipilimumab dosing may mitigate toxicity rates and positively impact quality of life without compromising efficacy, a hypothesis being explored in other tumour types such as non-small cell lung cancer. The best way to give this combination to patients with mRCC must be similarly established. Trial registration PRISM is registered with ISRCTN (reference ISRCTN95351638, 19/12/2017). Trial status At the time of submission, PRISM is open to recruitment and data collection is ongoing. |
| first_indexed | 2024-12-21T04:04:54Z |
| format | Article |
| id | doaj.art-62e16f703fca4bf2acf7b093a40e6f10 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-21T04:04:54Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-62e16f703fca4bf2acf7b093a40e6f102022-12-21T19:16:37ZengBMCBMC Cancer1471-24072019-11-011911910.1186/s12885-019-6273-1PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinomaHannah L. Buckley0Fiona J. Collinson1Gemma Ainsworth2Heather Poad3Louise Flanagan4Eszter Katona5Helen C. Howard6Geraldine Murden7Rosamonde E. Banks8Joanne Brown9Galina Velikova10Tom Waddell11Kate Fife12Paul D. Nathan13James Larkin14Thomas Powles15Sarah R. Brown16Naveen S. Vasudev17Clinical Trials Research Unit, University of LeedsClinical Trials Research Unit, University of LeedsClinical Trials Research Unit, University of LeedsClinical Trials Research Unit, University of LeedsClinical Trials Research Unit, University of LeedsClinical Trials Research Unit, University of LeedsClinical Trials Research Unit, University of LeedsClinical Trials Research Unit, University of LeedsLeeds Institute of Medical Research at St James’s, St. James’s University HospitalLeeds Institute of Medical Research at St James’s, St. James’s University HospitalUniversity of LeedsDepartment of Medical Oncology, Christie HospitalAddenbrooke’s HospitalMount Vernon Cancer CentreRoyal Marsden HospitalBarts Cancer InstituteClinical Trials Research Unit, University of LeedsLeeds Institute of Medical Research at St James’s, St. James’s University HospitalAbstract Background The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC) based on recent phase III data. Combining ipilimumab with nivolumab increases rates of grade 3 and 4 toxicity compared with nivolumab alone, and the optimal scheduling of these agents when used together remains unknown. The aim of the PRISM study is to assess whether less frequent dosing of ipilimumab (12-weekly versus 3-weekly), in combination with nivolumab, is associated with a favourable toxicity profile without adversely impacting efficacy. Methods The PRISM trial is a UK-based, open label, multi-centre, phase II, randomised controlled trial. The trial population consists of patients with untreated locally advanced or metastatic clear cell RCC, and aims to recruit 189 participants. Participants will be randomised on a 2:1 basis in favour of a modified schedule of 4 doses of 12-weekly ipilimumab versus a standard schedule of 4 doses of 3-weekly ipilimumab, both in combination with standard nivolumab. The proportion of participants experiencing a grade 3 or 4 adverse reaction within 12 months forms the primary endpoint of the study, but with 12-month progression free survival a key secondary endpoint. The incidence of all adverse events, discontinuation rates, overall response rate, duration of response, overall survival rates and health related quality of life will also be analysed as secondary endpoints. In addition, the potential of circulating and tissue-based biomarkers as predictors of therapy response will be explored. Discussion The combination of nivolumab with ipilimumab is active in patients with mRCC. Modifying the frequency of ipilimumab dosing may mitigate toxicity rates and positively impact quality of life without compromising efficacy, a hypothesis being explored in other tumour types such as non-small cell lung cancer. The best way to give this combination to patients with mRCC must be similarly established. Trial registration PRISM is registered with ISRCTN (reference ISRCTN95351638, 19/12/2017). Trial status At the time of submission, PRISM is open to recruitment and data collection is ongoing.http://link.springer.com/article/10.1186/s12885-019-6273-1Renal cancerNivolumabIpilimumabScheduleSafetyEfficacy |
| spellingShingle | Hannah L. Buckley Fiona J. Collinson Gemma Ainsworth Heather Poad Louise Flanagan Eszter Katona Helen C. Howard Geraldine Murden Rosamonde E. Banks Joanne Brown Galina Velikova Tom Waddell Kate Fife Paul D. Nathan James Larkin Thomas Powles Sarah R. Brown Naveen S. Vasudev PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma BMC Cancer Renal cancer Nivolumab Ipilimumab Schedule Safety Efficacy |
| title | PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma |
| title_full | PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma |
| title_fullStr | PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma |
| title_full_unstemmed | PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma |
| title_short | PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma |
| title_sort | prism protocol a randomised phase ii trial of nivolumab in combination with alternatively scheduled ipilimumab in first line treatment of patients with advanced or metastatic renal cell carcinoma |
| topic | Renal cancer Nivolumab Ipilimumab Schedule Safety Efficacy |
| url | http://link.springer.com/article/10.1186/s12885-019-6273-1 |
| work_keys_str_mv | AT hannahlbuckley prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT fionajcollinson prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT gemmaainsworth prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT heatherpoad prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT louiseflanagan prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT eszterkatona prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT helenchoward prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT geraldinemurden prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT rosamondeebanks prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT joannebrown prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT galinavelikova prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT tomwaddell prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT katefife prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT pauldnathan prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT jameslarkin prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT thomaspowles prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT sarahrbrown prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma AT naveensvasudev prismprotocolarandomisedphaseiitrialofnivolumabincombinationwithalternativelyscheduledipilimumabinfirstlinetreatmentofpatientswithadvancedormetastaticrenalcellcarcinoma |