Durvalumab in frail and elderly patients with stage four non-small cell lung cancer: Study protocol of the randomized phase II DURATION trial
Open Access
- 22 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Trials
- Vol. 21 (1), 1-12
- https://doi.org/10.1186/s13063-020-04280-8
Abstract
Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group. This prospective, open label, treatment stratified, randomized phase II study will enroll 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be aged 70 years or older and/or “frail” (Charlson Comorbidity Index > 1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG > 1). Patients are stratified according to modified Cancer and Age Research Group (CARG) score: “fit” patients are allocated to combination CT (carboplatin/nab-paclitaxel) and “less fit” patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either four cycles of CT or two cycles of CT followed by two cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks. The primary endpoint is the rate of treatment-related grade III/IV adverse events (Common Terminology Criteria for Adverse Events (CTCAE) V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential “frail” and “elderly” patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers. The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients. ClinicalTrials.gov, NCT03345810; initially registered on 17 November 2017. Eudra-CT, 2016–003963-20; initially registered on 3 January 2017.Other Versions
Funding Information
- Celgene
- AstraZeneca Schweiz
This publication has 47 references indexed in Scilit:
- Age is a prognostic factor affecting survival in lung cancer patientsOncology Letters, 2013
- Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in CancerThe New England Journal of Medicine, 2012
- Weekly nab-Paclitaxel in Combination With Carboplatin Versus Solvent-Based Paclitaxel Plus Carboplatin as First-Line Therapy in Patients With Advanced Non–Small-Cell Lung Cancer: Final Results of a Phase III TrialJournal of Clinical Oncology, 2012
- The blockade of immune checkpoints in cancer immunotherapyNature Reviews Cancer, 2012
- Predicting Chemotherapy Toxicity in Older Adults With Cancer: A Prospective Multicenter StudyJournal of Clinical Oncology, 2011
- Platinum-based drugs disrupt STAT6-mediated suppression of immune responses against cancer in humans and miceJCI Insight, 2011
- Potential role of immunosenescence in cancer developmentAnnals of the New York Academy of Sciences, 2010
- Lung Cancer in Elderly Patients: An Analysis of the Surveillance, Epidemiology, and End Results DatabaseJournal of Clinical Oncology, 2007
- Phase III Study of Docetaxel Compared With Vinorelbine in Elderly Patients With Advanced Non–Small-Cell Lung Cancer: Results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904)Journal of Clinical Oncology, 2006
- Developing a cancer‐specific geriatric assessmentCancer, 2005