scholarly journals 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 ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hannah L. Buckley ◽  
Fiona J. Collinson ◽  
Gemma Ainsworth ◽  
Heather Poad ◽  
Louise Flanagan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Phase Iii ◽  
First Line ◽  
Grade 3

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.

Phase II Study of Sunitinib Administered in a Continuous Once-Daily Dosing Regimen in Patients With Cytokine-Refractory Metastatic Renal Cell Carcinoma

2009 ◽  
Vol 27 (25) ◽  
pp. 4068-4075 ◽  
Author(s):  
Bernard Escudier ◽  
Jan Roigas ◽  
Silke Gillessen ◽  
Ulrika Harmenberg ◽  
Sandhya Srinivas ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Dosing Regimen ◽  
Once Daily ◽  
Grade 3

PurposeSunitinib has demonstrated antitumor activity in metastatic renal cell carcinoma (mRCC) when given at 50 mg/d on a 4-weeks-on 2-weeks-off regimen. Herein, we report results of an open-label, multicenter phase II mRCC study of sunitinib administered on a continuous once-daily dosing regimen.Patients and MethodsEligibility criteria included histologically proven mRCC with measurable disease, failure of one prior cytokine regimen, and good performance status. Patients were randomly assigned to a sunitinib starting dose of 37.5 mg/d in the morning (AM) or evening (PM). RECIST-defined objective response rate (ORR) was the primary end point. Secondary end points included progression-free survival (PFS), overall survival (OS), adverse events (AEs), and quality-of-life measures.ResultsOne hundred seven patients were randomly assigned to AM (n = 54) or PM (n = 53) dosing and on study for a median 8.3 months. Eighty-three patients discontinued, 65 due to disease progression and 16 because of AEs; two patients withdrew consent. Dosing was reduced to 25 mg/d in 46 patients (43%) due to grade 3/4 AEs. The most common grade 3 treatment-related AEs were asthenia/fatigue (16%), diarrhea (11%), hypertension (11%), hand-foot syndrome (9%), and anorexia (8%). ORR was 20% with a 7.2-month median response duration. Median PFS and OS were 8.2 and 19.8 months, respectively, at median follow-up of 26.4 months. Efficacy, tolerability, and quality-of-life results were similar between patients dosed in the AM or PM.ConclusionSunitinib 37.5 mg, administered on a continuous once-daily dosing regimen, has a manageable safety profile as second-line mRCC therapy, providing flexible dosing, which can be explored in combination studies.

Patient-reported outcomes in a randomized trial of everolimus with metastatic renal cell carcinoma patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17516-e17516
Author(s):  
J. Beaumont ◽  
D. Cella ◽  
T. Hutson ◽  
S. Bracarda ◽  
V. Grünwald ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Patient Reported Outcomes ◽  
Phase Iii ◽  
Patient Reported ◽  
Secondary Analyses

e17516 Background: Patient-reported outcomes (PRO), including health-related quality of life (HRQL), were assessed in a Phase III trial of everolimus in metastatic renal cell carcinoma (mRCC) patients. Methods: Patients with mRCC were randomized (n=416) to receive everolimus or placebo plus best supportive care. Patients completed the FACT-Kidney Symptom Index- Disease Related Symptoms (FKSI-DRS) and EORTC-QLQ C30 at baseline and monthly during treatment. Karnofsky Performance Status (KPS) was also assessed at baseline and monthly during treatment. Primary analyses included time to deterioration defined as a decrease from baseline of at least 3 points for FKSI-DRS, at least 10% for EORTC Physical Function (PF) and Global Quality of Life (QL) scales, and at least 10 points for KPS. Secondary analyses considered tumor progressions that occurred prior to deterioration or censoring date as FKSI deterioration events and compared time to PRO deterioration by tumor progression. Comparisons were made using stratified log-rank tests and Cox proportional hazard models. Results: Time to deterioration in KPS was longer in the everolimus arm, and time to deterioration in FKSI-DRS was slightly longer ( Table ). There was no difference in time to deterioration in PF or QL. Secondary analyses showed median time to deterioration in FKSI-DRS was approximately doubled for the everolimus arm compared to placebo, and patients who progressed experienced a more rapid deterioration in FKSI-DRS and QL scores. Conclusions: Compared to placebo everolimus delayed progression of disease-related symptoms and KPS. No effect on time to deterioration of PF or QL could be determined. Secondary analyses suggest a delay in deterioration in kidney cancer related symptoms via tumor control. [Table: see text] [Table: see text]

Quality of life assessment in renal cell carcinoma Phase II and III clinical trials published between 2010 and 2020: a systematic review

2021 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Filippo Gustavo Dall’Olio ◽  
Angela Dalia Ricci ◽  
Ilaria Maggio ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Life Assessment ◽  
Phase Iii ◽  
End Points

Aims: Quality of life (QoL) assessment is frequently not included among the end points of clinical trials (CTs) on renal cell carcinoma. Herein we aimed to describe the assessment and reporting of QoL in Phase II and Phase III CTs published between 2010 and 2020. Methods: A total of 25 CTs were included; 76% of trials included were conducted in metastatic renal cell carcinoma patients, while 20% of studies evaluated adjuvant systemic treatments. Results: In 13/25 publications, QoL was not listed among the end points, with secondary publications dedicated to QoL present in a minority of cases. Conclusions: QoL was not included among the end points of a large percentage of CTs. Implementing the inclusion of QoL represents an urgent need.

scholarly journals Quality of Life Predicts Progression-Free Survival in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib Versus Interferon Alfa

2009 ◽  
Vol 5 (2) ◽  
pp. 66-70 ◽  
Author(s):  
David Cella ◽  
Joseph C. Cappelleri ◽  
Andrew Bushmakin ◽  
Claudie Charbonneau ◽  
Jim Z. Li ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Free Survival

In a randomized phase III trial, sunitinib was associated with significantly superior progression-free survival when compared with interferon alfa as first-line therapy in patients with metastatic renal cell carcinoma. This article investigates whether baseline quality of life and demographic and clinical variables were predictive for progression-free survival.

Randomized phase II multicenter study of the efficacy and safety of sunitinib on the 4/2 versus continuous dosing schedule as first-line therapy of metastatic renal cell carcinoma: Renal EFFECT Trial.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. LBA308-LBA308 ◽  
Author(s):  
R. J. Motzer ◽  
T. E. Hutson ◽  
M. R. Olsen ◽  
G. R. Hudes ◽  
J. M. Burke ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Primary Endpoint ◽  
Renal Cell ◽  
Phase Iii ◽  
First Line ◽  
Randomized Phase Ii ◽  
Continuous Dosing

LBA308 Background: In a randomized phase III trial, sunitinib 50 mg/d on Schedule 4/2 (4 wk on treatment [Tx], 2 wk off) showed superior progression-free survival (primary endpoint) to IFN-α (11 vs. 5 mo; p<0.001) as first-line metastatic renal cell carcinoma (mRCC) therapy with a median overall survival (OS) of >2 yr (Motzer 2009). Continuous dosing of sunitinib 37.5 mg has demonstrated antitumor activity with a manageable safety profile in first- and second-line mRCC (Barrios; Escudier, 2009). Methods: This randomized phase II trial compared sunitinib 50 mg/d on Schedule 4/2 (Arm A) vs. 37.5 mg continuous once-daily dosing (Arm B) in first-line mRCC. Eligible patients (pts) had clear cell locally recurrent or mRCC; measurable disease; and Karnofsky performance status ≥70%. Randomization (1:1) was stratified by MSKCC risk groups. Sunitinib was continued until progression, unacceptable toxicity, or up to 2 yr. The primary endpoint was time to tumor progression (TTP) by Kaplan-Meier estimate. Secondary endpoints included objective response rate (ORR), OS, and adverse events (AEs). Results: Between January 2007 and June 2008, 292 pts were randomized. As of October 2010, 289 pts had received sunitinib, and all pts were off therapy. Median age was 62 yr. 65% were male. By MSKCC criteria, 28%, 61%, and 11% were favorable, intermediate, and poor risk, respectively. Pts received a median 4 and 5 Tx cycles in Arms A and B, respectively; median relative dose intensity was 90.8% and 77.5%. Dose delays, reductions, and interruptions occurred in 30% vs. 13%, 36% vs. 43%, and 65% vs. 62%, respectively; 11% and 15% discontinued due to Tx-related AEs. Median TTP was 9.9 vs. 7.1 mo in Arms A and B, respectively (HR=0.773, 95.1% CI, 0.572, 1.044; p=0.090). ORR was 32.2% vs. 28.1% (p=0.444). Median OS was 23.1 vs. 23.5 mo (p=0.615). The most common Tx-related AEs were fatigue (both 62%), nausea (56% vs. 49%), and diarrhea (56% vs. 64%). Conclusions: In this randomized phase II mRCC trial, there was a trend toward inferior TTP with continuous dosing. ORR, OS, and AE profiles were similar for the approved sunitinib 50 mg/d dose on Schedule 4/2 vs. 37.5 mg continuous dosing. [Table: see text]

Quality of Life in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib or Interferon Alfa: Results From a Phase III Randomized Trial

2008 ◽  
Vol 26 (22) ◽  
pp. 3763-3769 ◽  
Author(s):  
David Cella ◽  
Jim Z. Li ◽  
Joseph C. Cappelleri ◽  
Andrew Bushmakin ◽  
Claudie Charbonneau ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Least Squares ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Interferon Alfa ◽  
Phase Iii ◽  
Eq Vas

Purpose In an international, randomized phase III trial, sunitinib demonstrated statistically significant efficacy over interferon alfa (IFN-α) as first-line therapy in patients with metastatic renal cell carcinoma (mRCC) (progression-free survival time, 11 v 5 months, respectively; P < .001; objective response rate, 31% v 6%, respectively; P < .001). We report health-related quality-of-life (QOL) results from this trial. Patients and Methods Seven hundred fifty mRCC patients were randomly assigned to sunitinib (6-week cycles: 50 mg orally once daily for 4 weeks, followed by 2 weeks off) or IFN-α (9 million units subcutaneous injections, three times weekly). QOL measures included the Functional Assessment of Cancer Therapy–General (FACT-G), the FACT-Kidney Symptom Index–15 item (FKSI-15), and the EuroQoL-5D's utility score (EQ-5D Index) and its visual analog scale (EQ-VAS). The primary QOL end point was the FKSI Disease-Related Symptoms (FKSI-DRS) subscale. Higher scores indicated better outcomes (better QOL or fewer symptoms). Data were analyzed for the intent-to-treat population using mixed-effects models, supplemented with pattern-mixture models. Results Patients receiving sunitinib reported higher FKSI-15 and FKSI-DRS scores at each cycle than those receiving IFN-α, with a significant difference in the overall least squares means (3.27 and 1.98, respectively; P < .0001). Similarly, differences in least squares means for FACT-G (and all subscales), EQ-5D Index, and EQ-VAS were all significantly favorable for sunitinib (P < .01). Per pre-established thresholds, between-treatment differences in the mean scores were clinically meaningful after cycle 4 for FKSI-DRS and at all assessments for FKSI-15, FACT-G, and the FACT-G functional well-being subscale. Conclusion Sunitinib provides superior QOL compared with IFN-α in mRCC patients.

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