This study has been transitioned to CTIS with ID 2023-509576-42-00 check the CTIS register for the current data. This Phase III study, the administration of durvalumab + chemotherapy prior to surgery, followed by administration of durvalumab after…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- To compare the efficacy of durvalumab + chemotherapy administered prior to
surgery followed by durvalumab post-surgery compared with placebo +
chemotherapy administered prior to surgery followed by placebo post-surgery in
terms of EFS (event-free survival)
- To compare the activity of durvalumab + chemotherapy administered prior to
surgery compared with placebo + chemotherapy administered
prior to surgery in terms of mPR(major pathologic response = 10% or less
residual viable tumor tissue in lung primary tumor after neoadjuvant treatment
at the time of resection)
Secondary outcome
- To compare the efficacy of perioperative durvalumab + neoadjuvant
chemotherapy compared with placebo + neoadjuvant chemotherapy in
terms of DFS
- To compare the efficacy of perioperative durvalumab + neoadjuvant
chemotherapy compared with placebo + neoadjuvant chemotherapy in
terms of MPR
- To compare the efficacy of perioperative durvalumab + neoadjuvant
chemotherapy compared with placebo + neoadjuvant chemotherapy in
terms of OS
- To compare the efficacy of perioperative durvalumab + neoadjuvant
chemotherapy compared with placebo + neoadjuvant chemotherapy in
patients with PD-L1 TC >=1% tumors in terms of EFS, pCR, DFS, MPR and OS
- To assess disease-related symptoms and HRQOL in patients treated with
perioperative durvalumab + neoadjuvant chemotherapy compared
with placebo + neoadjuvant chemotherapy
- To assess the PK and immunogenicity of durvalumab
Background summary
Lung cancer has been the most common cancer in the world for several decades,
with an estimated 1.8 million new cases in 2012 (12.9% of all new cancers), and
was also the most common cause of death from cancer in 2012, with 1.6 million
deaths (19.4% of cancer deaths). NSCLC represents 80% to 85% of all lung
cancers. Despite advances in the diagnosis, imaging, staging, and treatment of
NSCLC, the estimated 5-year OS for patients in Europe and the United States
(US) continues to be low (11% and 17%, respectively).
For early-stage NSCLC, the primary treatment is curative surgery. Only ~30% of
patients present with Stages I to IIIA lung cancer; however, this percentage is
expected to increase as a result of the implementation of lung cancer
screening. Unfortunately, the 5-year survival for patients treated with surgery
alone remains low, ranging from 67% (Stage IA) to 23% (Stage IIIA).
Studies of adjuvant chemotherapy in the NSCLC setting have demonstrated a
modest but clinically meaningful improvement in OS; perioperative
platinum-based chemotherapy has shown a survival rate of 5.4 percentage points
higher than surgery alone, with toxicities of Grade 3 or higher observed in
more than 60% of patients.
A number of studies have demonstrated the clinical benefit of neoadjuvant
chemotherapy in early-stage NSCLC; major pathologic response (mPR) was observed
(improvement of the overall survival).
Despite these advances, new therapies are needed to further improve the
long-term prognosis for patients with NSCLC who undergo surgical resection.
Study objective
This study has been transitioned to CTIS with ID 2023-509576-42-00 check the CTIS register for the current data.
This Phase III study, the administration of durvalumab + chemotherapy prior to
surgery, followed by administration of durvalumab after surgery, will be
investigated in patients with resectable Stages II and III NSCLC. The efficacy
of durvalumab will be compared to a placebo group using event free survival
(EFS) and major pathologic response (mPR).
Study design
Phase Ill, double blinded, placebo-controlled, randomized study.
Randomisation 1:1 to:
- Durvalumab (IV) + platinum-based chemotherapy (4 cycles) before surgery +12
cycles durvalumab after surgery
- Placebo (IV) + platinum-based chemotherapy (4 cycles) before surgery +12
cycles placebo after surgery
Approximately 800 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):
- before surgery
* treatment group 1: patients receive (via IV infusion) 1500 mg durvalumab q3w
for up to a maximum of 4 cycles (+4 cycles platinum-based chemotherapy).
* treatment group 2: patients receive (via IV infusion) placebo q3w for up to a
maximum of 4 cycles (+4 cycles platinum-based chemotherapy).
- after surgery
* treatment group 1: patients receive (via IV infusion) 1500 mg durvalumab q4w
for 12 cycles
* treatment group 2: patients receive (via IV infusion) placebo q4w for 12
cycles
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
- pulmonary function tests and heart risk assessment
- biopsy (new biopt or <3 months old)
- surgery
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
- pain, scar tissue, infection, bleeding of the pneumothorax during biopsy
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Listed location countries
Age
Inclusion criteria
1. Age >=18 years 2. Newly diagnosed and previously untreated patients with
histologicallyor cytologically documented NSCLC with resectable (Stage IIA to
select [ie, N2] Stage IIIB) disease 3. World Health Organization (WHO)/ECOG PS
of 0 or 1 at enrollment 4. At least 1 lesion, not previously irradiated, that
qualifies as a RECIST 1.1 Target Lesion (TL) at baseline 5. No prior exposure
to immune-mediated therapy including, but not limited to, other anti-CTLA-4,
anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic
anticancer vaccines. 6. Adequate organ and marrow function 7. Confirmation of a
patients tumour PD-L1 status 8. Provision of sufficient tumour biopsy sample
for evaluation and confirmation of EGFR and ALK status 9. Planned surgery to be
performed need to include lobectomy, sleeve resection or bilobectomy.10. A pre-
or post-bronchodilator FEV of 1.0 L and >40% post-operative predicted value.
Exclusion criteria
1. History of allogeneic organ transplantation
2. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease, diverticulitis, systemic lupus erythematosus,
Sarcoidosis syndrome, or Wegener syndrome).
3. History of another primary malignancy
4. History of active primary immunodeficiency
5. . Active infection including tuberculosis hepatitis B and C, or human
immunodeficiency virus
6. Deemed unresectable NSCLC by multidisciplinary evaluation
7. Patients who have pre-operative radiotherapy treatment as part of their care
plan
8. Patients who have brain metastases or spinal cord compression
9. Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC
10. Known allergy or hypersensitivity to any of the study drugs or
excipients11. Existence of more than one primary tumour such as mixed small
cell and NSCLC histology12. Patients who are candidates to undergo only
pneumonectomy, segmentectomies or wedge resections.13. Patients with a
documented test result confirming the presence of EGFRm or ALK translocation.
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 |
|---|---|
| EU-CTR | CTIS2023-509576-42-00 |
| EudraCT | EUCTR2018-002997-29-NL |
| ClinicalTrials.gov | NCT03800134 |
| CCMO | NL72968.056.20 |