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Carcinoma, Non-Small-Cell LungPhase 3NVALT28NCT04597671

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

A Phase 3 study testing Durvalumab and low-dose PCI in people with Carcinoma, Non-Small-Cell Lung, run by Association NVALT Studies at 14 sites in Netherlands.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
Durvalumab and low-dose PCI
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
170 participants
Where
14 sitesNetherlands
Study dates
6 Dec 2021to Dec 2032
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must sign a study-specific informed consent
  • TNM8 stage IIIA, IIIB or IIIC non-small cell lung cancer before start of concurrent chemoradiotherapy (preferentially histology; cytology is allowed)
  • Whole body FDG-PET-scan and brain imaging (MRI or CT with iv contrast) before the start of chemoradiotherapy: No distant metastases.
  • Additional brain MRI (MRI mandatory) dated within 28 days before randomization: no brain metastases.
  • Eligible for durvalumab treatment according to registration label of durvalumab in the Netherlands. Durvalumab has to be given in standard of care. (durvalumab has to be started already before randomization and PCI (i.e. at least one administration of durvalumab has to be given before randomization).
  • Treatment completed with concurrent chemoradiation. The last day of chemoradiotherapy should be within 80 days of randomization and randomization should be after start of durvalumab. Any platinum doublet or daily cisplatin regimen that is standard of care in The Netherlands is allowed. No disease progression after chemoradiotherapy (evaluated with CT-thorax and upper abdomen during/after the last dose of chemoradiotherapy and comparison with CT before start of chemoradiotherapy). Consolidation chemotherapy cycles after radiotherapy is not permitted but administration of 1 cycle of chemotherapy prior to concurrent chemo-radiotherapy is acceptable. Where possible, chemotherapy regimens should be given according to National Comprehensive Cancer Network (NCCN) Guidelines or European Society for Medical Oncology (ESMO) Guidelines.
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  • To be eligible for randomization, patients must have received a total dose of thoracic radiotherapy of 60-66 Gy in 2 - 2.75 Gy per day, oncedaily fractions, or in case of daily cisplatin regimen 60.5-66 Gy in 22-24 fractions. Other radiotherapy schedules are not allowed. Sites are encouraged to adhere to the organ at risk constraints as used in the PACIFIC study as well as the EORTC recommendations for high-dose radiotherapy for lung cancer:
  • Mean lung dose must be <20 Gy and/or V20Gy must be <35%
  • Mean oesophagus dose must be <34 Gy
  • Heart V45Gy <35% or V30Gy <30%.
  • Proton therapy to the chest is allowed.
  • ECOG performance status 0-1 at the time of randomization.
  • Evidence of postmenopausal status, or negative urinary or serum pregnancy test for female premenopausal patients.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

Netherlands14 sites

  • ZGT

    Almelo

  • AmsterdamUMC - location VUmc

    Amsterdam

  • Radiotherapie Groep

    Arnhem

  • Rijnstate

    Arnhem

  • Gelderse Vallei

    Ede

  • Catharina Ziekenhuis

    Eindhoven

  • ZRTI

    Flushing

  • UMCG

    Groningen

  • Maastro

    Maastricht, 5912 BL

  • Canisius Wilhemina Ziekenhuis

    Nijmegen

  • Radboud UMC

    Nijmegen

  • ZorgSaam Ziekenhuis

    Terneuzen

  • Maxima Medisch Centrum

    Veldhoven

  • Zaans Medisch Centrum

    Zaandam

Other trials in Netherlands

About this study

Official title: 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

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.

Read the 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.

Being tested
Durvalumab, low-dose PCI
Keywords
PCI, immunotherapy, NSCLC, QoL
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DurvalumabDrug

    Also called Imfinzi

    Durvalumab is used as standard of care

  • low-dose PCIRadiation

    Also called Prophylactic Cranial Irradiation (PCI)

    PCI will be given concurrently with durvalumab. PCI will be given to a dose of 15 Gy in 10 fractions

Study groups in NCT04597671
Study groupRoleWhat they receive
Arm AExperimentalDurvalumab with low-dose PCI
Receives: Drug: Durvalumab; Radiation: low-dose PCI
Arm BActive comparatorDurvalumab with observation
Receives: Drug: Durvalumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reduction of incidence of brain metastases

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

    Measured: From randomisation until moment of discovery of brain metastases or latest at 24 months after randomization

Secondary outcomes (5)

  1. Effect on neurocognitive functioning

    To evaluate what the effect is on neurocognitive functioning to be meassured with HVLT-R carried out by hospital staff.

    Measured: From randomization until 24 months after randomization

  2. Time to develop neurological symptoms

    To evaluate time to develop neurological symptoms (CTCAE version 5.0)

    Measured: From randomization until time to develop neurological symptoms with a maximum of 24 months after randomization

  3. Toxicity assessment

    To evaluate adverse events (CTCAE v 5.0 and PRO-CTCAE) that is the result of study treatment

    Measured: From randomization until end of study treatment

  4. Patient reported neurocognitive decline

    To evaluate patient reported neurocognitive decline using PRO-CTCAE (patient reported outcome)

    Measured: From randomization until 5 years after randomization

  5. Cost-efficiency

    To evaluate cost-efficiency of the addition of PCI to durvalumab with a state-transition model, calculated with Dutch tariff

    Measured: From randomization until end of study treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Oct 2020
  2. Study start6 Dec 2021
  3. Primary completionDec 2028 (estimated)
  4. Study completionDec 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
170 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04597671
Sponsor's protocol ID
NVALT28
Acronym
NVALT28
Status last verified
Jan 2025
First submitted
24 Sep 2020
Last updated
29 Jan 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Durvalumab and low-dose PCI in people with Carcinoma, Non-Small-Cell Lung, run by Association NVALT Studies at 14 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reduction of incidence of brain metastases (time frame: From randomisation until moment of discovery of brain metastases or latest at 24 months after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04597671.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2025.

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