The research hypothesis for this study is that concurrent durvalumab plus SoC chemotherapy will be more effective than placebo plus SoC chemotherapy for the treatment of MRD+ patients who have undergone complete resection of stage II-III NSCLC when…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the efficacy of durvalumab + SoC chemotherapy compared to placebo +
SoC chemotherapy as measured by DFS in MRD+ patients
Secondary outcome
- To assess the efficacy of durvalumab plus SoC chemotherapy compared to
placebo plus SoC chemotherapy as measured by DFS in all patients
- To assess the efficacy of durvalumab plus SoC chemotherapy compared to
placebo plus SoC chemotherapy as measured by DFS in MRD+ patients and all
patients
- To assess the efficacy of durvalumab plus SoC chemotherapy compared to
placebo plus SoC chemotherapy as measured by OS in MRD+ patients and in all
patients
- To assess patient-reported symptoms, functioning, and HRQoL in MRD+ patients
treated with durvalumab plus SoC chemotherapy compared to placebo plus SoC
chemotherapy
Background summary
Up to 30% of patients with NSCLC present with surgically resectable disease.
For patients with stage II-IIIA and select IIIB disease, surgery and adjuvant
SoC chemotherapy results in 5-year disease-free survival (DFS) rates of only
~40%. The majority of patients who remain event-free at 5 years are cured by
surgery alone yet receive adjuvant treatment because there is currently no
clear way to determine who will benefit from adjuvant chemotherapy.
There is evidence that identification of MRD through detection of ctDNA
post-surgery can accurately predict disease recurrence. Detection of MRD at a
time when there is no radiologic evidence of disease provides an opportunity
for earlier therapeutic intervention. Patients with MRD (MRD-positive [MRD+])
experience inferior recurrence-free survival compared to patients without
detectable MRD (MRD-negative [MRD-]). Therefore, MRD+ patients could benefit
from earlier intervention and escalation of treatment; furthermore, MRD-
patients (the majority of whom are cured by surgery alone) could be spared from
more intensive therapy and the resulting unnecessary toxicity.
Clinical data suggest that the combination of immunotherapy and chemotherapy in
the adjuvant setting, where patients have undergone a complete resection but
may have residual disease, would provide additional benefits to single agent
immunotherapy and improve DFS.
Study objective
The research hypothesis for this study is that concurrent durvalumab plus SoC
chemotherapy will be more effective than placebo plus SoC chemotherapy for the
treatment of MRD+ patients who have undergone complete resection of stage
II-III NSCLC when administered in the adjuvant setting.
Study design
Phase Ill, double blinded, placebo-controlled, randomized study.
Randomisation 1:1 to:
- Durvalumab (IV) + platinum-based chemotherapy (4 cycles) +10 cycles durvalumab
- Placebo (IV) + platinum-based chemotherapy (4 cycles) +10 cycles placebo
323 patients will receive treatment upon progression, followed by FU-fase.
Intervention
Patients will receive (unless there is unacceptable toxicity, withdrawal of
consent, or another discontinuation criterion is met):
* treatment group 1: patients receive (via IV infusion) 1500 mg durvalumab +
SoC chemotherapy q3w for 4 cycles + 10 cycles 1500 mg durvalumab
* treatment group 2: patients receive (via IV infusion) placebo q3w +SoC
chemotherapy for 4 cycles + 10 cycles placebo.
Study burden and risks
Patiënts are subject to the following assessments throughout the study:
- Anamnesis (at screening, including medical history)
- Physical examination
- ECOG performance status
- Vital functions (blood pressure, heartrate, body temperature and respiratory
rhythm)
- Body weight measurement
- brain MRI/CT scan with IV contrast (only at screening)
- ECG
- blood- and urine examination
- questionnaires (EORTC QLQ-C30, EORTC QLQ-LC13, EQ-5D-5L, PGIS, PRO-CTCAE)
- pregnancy test when applicable
- AE/SAE assessment
- IP administration
- CT+PET scan at screening for staging purposes and as pre-operative assessment
- heart risk assessment
- surgery
- During screening, if there is no "tumor tissue", residual material, may be
used to determine markers.
Durvalumab activates the immune system of the body and this can cause adverse
effects. Adverse effects can arise during or within
several hours/days after the administration of the IV line. The adverse effects
that are known, are obtained from previous studies. It
is possible that the patient might suffer from 1 or all of the following
adverse effects: fever, fatigue, rash or hives, change in blood
pressure, decrease in the amount of thrombocytes, inflammation of the lungs,
inflammation of the nervous system, inflammation of
the pancreas, inflammation of the liver, inflammation of the intestines,
changes in nodes that regulate hormone production.
Chemotherapy can also cause adverse effects.
The adverse effects can vary from mild to severe and can even be
life-threatening. In this study certain conditions are incorporated
for early signalling of these severe adverse effects. Moreover, the study
procedures might also cause the following ailments:
- pain or bruises through collection of blood
- rash through ECG stickers
- health risks through radiation of CT-scan/MRI
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Listed location countries
Age
Inclusion criteria
• Individuals who have diagnosis of histologically confirmed NSCLC (WHO 2015
classification) with resectable (stage II-III) disease
• A contrast-enhanced CT/MRI scan of the chest and abdomen (including liver and
adrenal glands) must have been done for surgical planning prior to surgery
• Complete resection of the primary NSCLC is mandatory
• Confirmation of suitable resected tumor tissue and whole blood sample
• Post-operative CT scan of the chest and abdomen
• Adequate organ and marrow function
• Eligible to tolerate 4 cycles of platinum-based adjuvant chemotherapy
• Must have a life expectancy of at least 12 weeks
Exclusion criteria
• Unequivocal evidence of disease recurrence or tissue biopsy-proven disease
recurrence
• EGFR-mutant and/or ALK-translocation
• Mixed small cell and NSCLC histology
• Require re-resection or are deemed to have unresectable NSCLC by a
multidisciplinary evaluation that must include a thoracic surgeon who performs
lung cancer surgery as a significant part of their practice.
• Patients who are candidates to undergo only wedge resections
• Active or prior documented autoimmune or inflammatory disorders
• Uncontrolled intercurrent illness (see protocol page 67)
• History of another primary malignancy (check for exceptions)
• History of active primary immunodeficiency
• Active infection including tuberculosis, hepatitis B, hepatitis C virus or HIV
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer
treatment (check for exceptions)
• Current or prior use of immunosuppressive medication within 14 days before
the first dose of durvalumab (check for exceptions)
• Patients who are never-smokers
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2020-000556-35-NL |
| ClinicalTrials.gov | NCT04385368 |
| CCMO | NL73257.056.20 |