Durvalumab and Low-dose PCI vs Durvalumab and Observation in Radically Treated Patients With Stage III NSCLC (NVALT28)
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Radiation: low-dose PCI
- Registration Number
- NCT04597671
- Lead Sponsor
- Association NVALT Studies
- Brief 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 170
Not provided
- Participation in another clinical study with an investigational product during the last 4 weeks.
- Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or a study that will not influence the primary and secondary endpoint parameters (e.g. bioimpedance measurements, E-Nose) or the follow-up period of an interventional study. Note: participation in the NVALT31 study (follow up with CT thorax or PET-CT) is allowed
- Mixed small cell and non-small cell lung cancer histology.
- Patients who receive sequential chemoradiation therapy for locally advanced NSCLC.
- Disease progression after completion of definitive platinum based, concurrent chemoradiation therapy, as proven by a CT scan after end of chemoradiation.
- Any unresolved toxicity CTCAE (v. 5.0) more than grade 2 (i.e. grade 3 or higher) from the prior chemoradiation therapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by PCI may be included (e.g. hearing loss) after consultation with the principal investigator.
- Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
- Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients with vitiligo, Grave's disease, diabetes type I or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- Active or prior documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis).
- History of primary immunodeficiency.
- History of organ transplant that requires therapeutic immunosuppression.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses or psychiatric illness/ social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent.
- Known history of tuberculosis, hepatitis B, hepatitis C or Human Immunodeficiency Virus (HIV).
- History of another primary malignancy within 2 years prior to starting study drug, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study.
- Prior cranial irradiation is not allowed.
- Except for durvalumab after concurrent chemoradiotherapy, no previous treatment with PD-(L)1-inhibitors is allowed.
- Female patients who are pregnant, breastfeeding or male or female patients of reproductive potential who are not employing an effective method of birth control.
- Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of patient safety or study results.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A Durvalumab Durvalumab with low-dose PCI Arm A low-dose PCI Durvalumab with low-dose PCI Arm B Durvalumab Durvalumab with observation
- Primary Outcome Measures
Name Time Method Reduction of incidence of brain metastases From randomisation until moment of discovery of brain metastases or latest at 24 months after randomization To evaluate whether the addition of PCI to durvalumab after concurrent chemo-radiotherapy for stage III NSCLC reduces the cumulative incidence of brain metastases.
- Secondary Outcome Measures
Name Time Method Effect on neurocognitive functioning From randomization until 24 months after randomization To evaluate what the effect is on neurocognitive functioning to be meassured with HVLT-R carried out by hospital staff.
Time to develop neurological symptoms From randomization until time to develop neurological symptoms with a maximum of 24 months after randomization To evaluate time to develop neurological symptoms (CTCAE version 5.0)
Toxicity assessment From randomization until end of study treatment To evaluate adverse events (CTCAE v 5.0 and PRO-CTCAE) that is the result of study treatment
Patient reported neurocognitive decline From randomization until 5 years after randomization To evaluate patient reported neurocognitive decline using PRO-CTCAE (patient reported outcome)
Cost-efficiency From randomization until end of study treatment To evaluate cost-efficiency of the addition of PCI to durvalumab with a state-transition model, calculated with Dutch tariff
Trial Locations
- Locations (14)
Zaans Medisch Centrum
🇳🇱Zaandam, Netherlands
ZGT
🇳🇱Almelo, Netherlands
AmsterdamUMC - location VUmc
🇳🇱Amsterdam, Netherlands
Radiotherapie Groep
🇳🇱Arnhem, Netherlands
Radboud UMC
🇳🇱Nijmegen, Netherlands
ZRTI
🇳🇱Vlissingen, Netherlands
Rijnstate
🇳🇱Arnhem, Netherlands
Gelderse Vallei
🇳🇱Ede, Netherlands
Catharina Ziekenhuis
🇳🇱Eindhoven, Netherlands
UMCG
🇳🇱Groningen, Netherlands
Maastro
🇳🇱Maastricht, Netherlands
Canisius Wilhemina Ziekenhuis
🇳🇱Nijmegen, Netherlands
ZorgSaam Ziekenhuis
🇳🇱Terneuzen, Netherlands
Maxima Medisch Centrum
🇳🇱Veldhoven, Netherlands