Comparing Impact of Treatment Before or After Surgery in Patients With Stage II-IIIB Resectable Non-small Cell Lung Cancer

Registration Number
NCT06632327
Lead Sponsor
Alliance for Clinical Trials in Oncology
Brief 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 befo...

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:
...

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
1100
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

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Exclusion Criteria

Not provided

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm 1 (surgery, adjuvant therapy)Surgical ProcedureSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)CisplatinSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)CarboplatinSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)Computed TomographySURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)Magnetic Resonance ImagingSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)Positron Emission TomographySURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)Surgical ProcedureNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)Computed TomographyNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)Magnetic Resonance ImagingNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)Positron Emission TomographyNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)GemcitabineSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)DocetaxelSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)PemetrexedSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)VinorelbineSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)NivolumabSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)PembrolizumabSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 1 (surgery, adjuvant therapy)AtezolizumabSURGERY: 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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)CisplatinNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)CarboplatinNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)GemcitabineNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)DocetaxelNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)VinorelbineNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)PemetrexedNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)NivolumabNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)PembrolizumabNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)AtezolizumabNEOADJUVANT 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 CT throughout the study and may undergo MRI and/or PET/CT at screening.
Primary Outcome Measures
NameTimeMethod
3-year real-world event-free survival (rwEFS)From the date of randomization to the date of the first of the following events: failure to undergo resection for any reason, recurrence or progression at any time after surgery, or death from any cause, assessed at 3 years

Time to event analyses will be summarized using the Kaplan-Meier method, where both the stratified and unstratified log-rank test will be used to compare the distributions across the treatment arms. For the primary analysis of 3-year rwEFS rate, we will compare the rwEFS curves at 3 years, using the difference in Kaplan-Meier estimates for the survival funct...

Overall survival (OS)From randomization until death from any cause, assessed up to 10 years

Time to event analyses will be summarized using the Kaplan-Meier method, where both the stratified and unstratified log-rank test will be used to compare the distributions across the treatment arms. OS rates at 1 year, 2 years, and 5 years will also be reported, along with 95% confidence intervals.

Secondary Outcome Measures
NameTimeMethod
Rates of surgical resectionUp to 10 years.

Rates of resection will be tabulated and compared between the arms using chi-square tests or Fisher's exact tests. Univariable Cox models stratified by the stratification factors used in the randomization will be used to understand the impact of baseline covariates, resection status and systemic treatments on outcomes.

Rates of complete resection (R0)Up to 10 years.

Rates of R0 resection will be tabulated and compared between the arms using chi-square tests or Fisher's exact tests. Univariable Cox models stratified by the stratification factors used in the randomization will be used to understand the impact of baseline covariates, resection status and systemic treatments on outcomes.

Incidence of adverse events (AEs)Up to 10 years.

Adverse events will be recorded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 for each patient. Frequency tables and summary statistics will be used to determine the overall patterns within and across the arms.

Pathological complete response (pCR)Up to 10 years

Pathologic complete response is defined as having no viable invasive cancer in the lung and lymph nodes (ypT0 ypN0 or ypT0/is ypN0) based on guidelines published by National Comprehensive Cancer Network and International Association for the Study of Lung Cancer. Cox regression models will be used to evaluate the association between pCR and rwEFS in periopera...

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