Trial Title:
Comparing Impact of Treatment Before or After Surgery in Patients With Stage II-IIIB Resectable Non-small Cell Lung Cancer
NCT ID:
NCT06632327
Condition:
Resectable Lung Non-Small Cell Carcinoma
Stage II Lung Cancer AJCC v8
Stage IIIA Lung Cancer AJCC v8
Stage IIIB Lung Cancer AJCC v8
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Carboplatin
Gemcitabine
Pembrolizumab
Docetaxel
Nivolumab
Pemetrexed
Atezolizumab
Vinorelbine
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Surgical Procedure
Description:
undergo surgery
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Intervention type:
Drug
Intervention name:
Cisplatin
Description:
Give cisplatin
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Give Carboplatin
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
Give Pemetrexed
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Intervention type:
Drug
Intervention name:
Gemcitabine
Description:
Give Gemcitabine
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Intervention type:
Drug
Intervention name:
Docetaxel
Description:
Give Docetaxel
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Intervention type:
Drug
Intervention name:
Vinorelbine
Description:
Give Vinorelbine
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Intervention type:
Drug
Intervention name:
Nivolumab
Description:
Give Nivolumab
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Give Pembrolizumab
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Give Atezolizumab
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT and/or PET/CT
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Other name:
CT Scan
Other name:
CAT Scan
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Other name:
MRI
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT
Arm group label:
Arm 1 (surgery, adjuvant therapy)
Arm group label:
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)
Other name:
PET Scan
Summary:
This phase III trial compares standard therapy given after surgery (adjuvant) to standard
therapy given before and after surgery (perioperative) in treating patients with stage
II-IIIB non-small cell lung cancer (NSCLC) that can be removed by surgery (resectable).
The usual approach for patients with resectable NSCLC is chemotherapy and/or
immunotherapy before surgery, after surgery, or both before and after surgery. This study
is being done to find out which approach is better at treating patients with lung cancer.
Treatment will be administered according to the current standard of care at the time of
enrollment. Chemotherapy options may include cisplatin, carboplatin, pemetrexed,
gemcitabine, docetaxel, and vinorelbine at standard doses according to the treating
physician. Cisplatin is in a class of medications known as platinum-containing compounds.
It works by killing, stopping or slowing the growth of tumor cells. Carboplatin is in a
class of medications known as platinum-containing compounds. It works in a way similar to
the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin
works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class
of medications called antifolate antineoplastic agents. It works by stopping cells from
using folic acid to make deoxyribonucleic acid (DNA) and may kill tumor cells.
Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill
tumor cells. Docetaxel is in a class of medications called taxanes. It stops tumor cells
from growing and dividing and may kill them. Other chemotherapy drugs, such as
vinorelbine, work in different ways to stop the growth of tumor cells, either by killing
the cells, by stopping them from dividing, or by stopping them from spreading .
Immunotherapy with monoclonal antibodies, such as nivolumab, pembrolizumab, and
atezolizumab, may help the body's immune system attack the tumor, and may interfere with
the ability of tumor cells to grow and spread. Starting treatment with chemotherapy and
immunotherapy prior to surgery and continuing treatment after surgery may be a more
effective treatment option than adjuvant therapy alone in patients with stage II-IIIB
resectable NSCLC.
Detailed description:
The primary and secondary objectives of the study:
PRIMARY OBJECTIVE:
I. To compare the 3-year real-world event-free survival (rwEFS) rate and overall survival
(OS) between perioperative and adjuvant immunotherapy-based treatment for patients with
resectable non-small cell lung cancer (dual endpoints).
SECONDARY OBJECTIVES:
I. To compare the rates of surgical resection between the two arms. II. To compare the
rates of complete resection (R0) between the two arms. III. To summarize and compare
rates of adverse events (AEs) resulting in permanent treatment discontinuation,
hospitalization, or death between the two arms.
IV. To evaluate the association between locally defined pathological complete response
(pCR) and rwEFS in patients randomized to the perioperative arm (arm 2).
V. To compare the rwEFS post 3-years from randomization between the two arms among
patients who do not experience an event by 3 years.
EXPLORATORY OBJECTIVES:
I. To compare outcomes according to the systemic therapy administered on each arm.
II. To compare the sites of relapse between the two treatment arms.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM 1:
SURGERY: Patients undergo surgery within 28 days of registration.
ADJUVANT THERAPY: Patients receive platinum-based doublet chemotherapy (cisplatin,
carboplatin, pemetrexed, gemcitabine, docetaxel, and/or vinorelbine) for up to 4 cycles
and immune checkpoint inhibitor therapy (nivolumab, pembrolizumab, and/or atezolizumab)
for up to 1 year in the absence of disease progression or unacceptable toxicity according
to current approved guidelines.
ARM 2:
NEOADJUVANT THERAPY: Within 28 days of registration, patients receive platinum-based
doublet chemotherapy (cisplatin, carboplatin, pemetrexed, gemcitabine, docetaxel, and/or
vinorelbine) for up to 4 cycles in combination with immune checkpoint inhibitor
(nivolumab, pembrolizumab, and/or atezolizumab) according to current approved guidelines.
SURGERY: Patients undergo surgery.
ADJUVANT THERAPY: Patients receive immune checkpoint inhibitor therapy (nivolumab,
pembrolizumab, and/or atezolizumab) for up to 1 year in the absence of disease
progression or unacceptable toxicity according to current approved guidelines.
Patients also undergo computed tomography (CT) throughout the study and may undergo
magnetic resonance imaging (MRI) and/or positron emission tomography (PET)/CT at
screening.
After completion of study treatment, patients are followed up every 6 months for up to 10
years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically or cytologically confirmed surgically resectable stage IIA to IIIB
NSCLC according to the American Joint Committee on Cancer (AJCC) 9th edition (stage
IIA to IIIB NSCLC up to single station N2, according to the AJCC 8th edition)
* Note: Patients with resectable stage N2a or T4 are eligible, but patients with
stage N2b or N3 are not eligible. Patients with known EGFR or ALK alterations are
excluded
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (or Karnofsky ≥
60%)
- No prior systemic treatment for NSCLC within 5 years except stage 1 and 2 cancers
treated with curative intent
- No treatment for another malignancy within 3 years prior to registration, except for
stage 1 or 2 cancers treated for curative intent; patients must be disease free for
one year prior to registration. Patients with non-melanoma skin cancer, urothelial
carcinoma in situ (Tis), noninvasive papillary carcinoma of the urinary bladder
(Ta), prostatic intraepithelial neoplasia (PIN), ductal carcinoma in situ (DCIS) of
the breast, or cervical intraepithelial neoplasia (CIN) of the uterine cervix are
also eligible
- No active autoimmune disease, interstitial lung disease, or transplant that
precludes safe treatment with immune checkpoint inhibitors
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral
load within 6 months are eligible for this trial
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
May 30, 2025
Completion date:
April 30, 2030
Lead sponsor:
Agency:
Alliance for Clinical Trials in Oncology
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Alliance for Clinical Trials in Oncology
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06632327
