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
NVALT-28
Study site
Principle Investigator
L. Hendriks (MUMC)
Investigator Maastro
D. DeRuysscher
Sponsor
NVALT
Trial registry
Objectives 

Primary:
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

Secondary:
•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.

Exploratory:
•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

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