NCT04597671

Durvalumab and Low-dose PCI vs Durvalumab and Observation in Radically Treated Patients With Stage III NSCLC (NVALT28)

NVALT 28/ 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

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 170 (estimated)
• Sponsor: Association NVALT Studies · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This trial studies the combination of low-dose PCI with or without durvalumab in patients with radically treated stage III NSCLC. The hypothesis is that the incidence of brain metastases will be reduced from 30% to 15 % with durvalumab and to a maximum of 5% with the addition of low-dose PCI. This strategy would make brain metastases in stage III NSCLC history and this would improve QoL.

Detailed description

The brain is frequently a site of disease relapse in Non-Small Cell Lung Cancer (NSCLC) patients. For radically treated patients, stage III has the highest risk for brain metastases with a cumulative incidence of brain metastases after radical treatment of approximately 30% for which there is no cure at the moment, decreasing the long-term survival and Quality of Life. Strategies to reduce incidence of brain metastases are necessary. Prophylactic Cranial Irradiation (PCI) has been shown to reduce the incidence of brain metastases in patients with NSCLC. However, PCI leads to a neurocognitive impairment in about 25% of patients without altering the QoL. The addition of durvalumab after chemo-radiotherapy in stage III NSCLC could reduce the incidence of brain metastases. In pre-clinical models, immunotherapy potentiates the effects of radiotherapy by a factor two to five. This makes the combination of PCI and immunotherapy interesting to evaluate whether it can further decrease the percentage of brain metastases as well as preserve organ function as a lower radiation dose can probably be used when combined with an antiprogrammed death (ligand)1 (PD(L)-1). The hypothesis of the NVALT28 trial is that the combination of PCI with durvalumab will decrease the incidence of brain metastases from 30% to 15 % with durvalumab and to a maximum of 5% with the addition of low-dose PCI. This strategy would make brain metastases in stage III NSCLC history and this would improve QoL.

Conditions

• Carcinoma, Non-Small-Cell Lung

Interventions

Type	Name	Description
DRUG	Durvalumab	Durvalumab is used as standard of care
RADIATION	low-dose PCI	PCI will be given concurrently with durvalumab. PCI will be given to a dose of 15 Gy in 10 fractions

Timeline

• Start date: 2021-12-06
• Primary completion: 2028-12-01
• Completion: 2032-12-01
• First posted: 2020-10-22
• Last updated: 2025-01-29

Locations

14 sites across 1 country: Netherlands