Cancer types
  • Lung
Title of study
NVALT28/PRL01 Durvalumab and low-dose Prophylactic Cranial Irradiation (PCI) versus durvalumab and observation in radically treated patients with stage III non-small cell lung cancer: A phase III randomized study
Version Number
Approval Date 
1.1, 16 Marchy 2021
Short Title
Study site
Principle Investigator
L. Hendriks (MUMC)
Investigator Maastro
D. DeRuysscher
Trial registry

To evaluate whether the addition of low dose PCI to durvalumab after concurrent chemo-radiotherapy for stage III NSCLC reduces the cumulative incidence of brain metastases

•Key secondary objective: to evaluate what the effect is on learning (using the HVLT-Rtotal recallscore) with the addition oflow-dose PCI to durvalumab after concurrent chemoradiation (CCRT) •To evaluate time to develop neurological symptoms -To evaluate the incidence and severity of neurological / fatigue adverse events (Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 and patient reported outcome (PRO)-CTCAE), the effect on QoL and the effect on OS and Quality Adjusted Life Years (QALYs) for low-dose PCI plus durvalumab versus durvalumab alone
•To evaluate patient reported neurocognitive decline -To evaluate cost-efficiency of the addition of low-dose PCI to durvalumab.

•To evaluate the effect of durvalumab with or without low-dose PCI on brain injury: neurofilaments and other markers in the blood (also in relation to neurocognitive tests)
•To evaluate the effect of durvalumab with or without low-dose PCI on other neurocognitive functions measured with the Amsterdam Cognition Scan test battery
•To evaluate the effect of durvalumab with or without low-dose PCI on immune markers and LC3/GABARAPL protein family in the blood
•Obtaining blood samples for cell-free DNA (cfDNA) for determining minimal residual disease (+ bio-banking blood samples for future translational research)
•Obtaining tumor material to investigate prognostic markers on standard diagnostic material
•Obtaining imaging (standard 18-Fluodeoxyglucose positron emission tomography (18FDG-PET), chest-computed tomographies (CTs) and brain Magnetic Resonance Imaging (MRI)s) for qualitative and quantitative image analyses
•To evaluate the effect of durvalumab on the cardiac function: B-type natriuretic pep-tide (BNP), Troponins, blood pressure, heart frequency/ rhythm, measured with an Electrocardiogram (ECG)
•To evaluate the effect of durvalumab on cancer associated skeletal muscle-and adipose tissue changes

Primary Endpoint 

Cumulative incidence of brain metastases 24 months after randomization.

Secondary Endpoints 

•Time to 5 points or more decline in the HVLT-R total recall compared to baseline (first: 4 months compared to baseline, additional: every year compared to baseline).
•Time to develop neurological symptoms (confirmed or unconfirmed by imaging) -Side effects: decline in ECOG performance status and CTCAE v. 5.0(neurological/fatigue) as well as Pro-CTCAE
•Patient reported neurocognitive memory decline -QoL: QLQ-C30 and EuroQol 5D-Overall survival
•Quality adjusted survival (QALYs)
•Health care costs