Trials Today

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

Purpose

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.

Conditions

Resectable Lung Non-Small Cell Carcinoma
Stage II Lung Cancer AJCC v8
Stage IIIA Lung Cancer AJCC v8
Stage IIIB Lung Cancer AJCC v8

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: All
Accepts Healthy Volunteers: No

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

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Arm 1 (surgery, adjuvant therapy)	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. Patients also undergo CT throughout the study and may undergo MRI and/or PET/CT at screening.	Procedure: Surgical Procedure undergo surgery Drug: Cisplatin Give cisplatin Drug: Carboplatin Give Carboplatin Drug: Pemetrexed Give Pemetrexed Drug: Gemcitabine Give Gemcitabine Drug: Docetaxel Give Docetaxel Drug: Vinorelbine Give Vinorelbine Drug: Nivolumab Give Nivolumab Drug: Pembrolizumab Give Pembrolizumab Drug: Atezolizumab Give Atezolizumab Procedure: Computed Tomography Undergo CT and/or PET/CT Other names: CT Scan CAT Scan Procedure: Magnetic Resonance Imaging Undergo MRI Other names: MRI Procedure: Positron Emission Tomography Undergo PET/CT Other names: PET Scan
Experimental Arm 2 (neoadjuvant therapy, surgery, adjuvant therapy)	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 CT throughout the study and may undergo MRI and/or PET/CT at screening.	Procedure: Surgical Procedure undergo surgery Drug: Cisplatin Give cisplatin Drug: Carboplatin Give Carboplatin Drug: Pemetrexed Give Pemetrexed Drug: Gemcitabine Give Gemcitabine Drug: Docetaxel Give Docetaxel Drug: Vinorelbine Give Vinorelbine Drug: Nivolumab Give Nivolumab Drug: Pembrolizumab Give Pembrolizumab Drug: Atezolizumab Give Atezolizumab Procedure: Computed Tomography Undergo CT and/or PET/CT Other names: CT Scan CAT Scan Procedure: Magnetic Resonance Imaging Undergo MRI Other names: MRI Procedure: Positron Emission Tomography Undergo PET/CT Other names: PET Scan

Recruiting Locations

University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233

Contact:
Site Public Contact
205-934-0220
tmyrick@uab.edu

Mercy Hospital Fort Smith
Fort Smith, Arkansas 72903

Contact:
Site Public Contact
800-378-9373

CARTI Cancer Center
Little Rock, Arkansas 72205

Contact:
Site Public Contact
501-906-4199
Research@CARTI.com

Kaiser Permanente-Deer Valley Medical Center
Antioch, California 94531