Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Dermatologic Agents

Micronutrients

Hematinics

Vitamins

Paclitaxel

Albumin-Bound Paclitaxel

Atezolizumab

Carboplatin

Etoposide

Pemetrexed

Cisplatin

Immunomodulating Agents

Etoposide phosphate

Podophyllotoxin

Folic Acid Antagonists

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Keratolytic Agents

Folinic Acid

Folate

Vitamin B9

Patients receive atezolizumab IV over 30-60 minutes on day 1. Patients also receive one of the chemotherapy combinations below depending on their previous therapy and disease. Between the first day of chemotherapy and the first day of cycle 2 of chemotherapy, patients undergo external beam radiation therapy 5 days per week. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 21 and 90 days after treatment, patients undergo surgery. Within 42 days after completion of surgery, patients then receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo a PET scan, CT scan, and MRI on study. Patients also undergo tumor biopsies and blood sample collection throughout the trial.

Patients receive one of the chemotherapy combinations below depending on their previous therapy and disease. Between the first day of chemotherapy and the first day of cycle 2 of chemotherapy, patients also undergo external beam radiation therapy 5 days per week. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 21 and 90 days after treatment, patients undergo surgery. Patients may undergo a PET scan, CT scan, and MRI on study. Patients also undergo tumor biopsies and blood sample collection throughout the trial.

Biopsy

Biospecimen Collection

Computed Tomography

External Beam Radiation Therapy

Magnetic Resonance Imaging

Positron Emission Tomography

Therapeutic Conventional Surgery

Raymond U Osarogiagbon

This phase II trial tests the effect of atezolizumab given with usual chemotherapy during radiation therapy in treating patients with superior sulcus non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as cisplatin, carboplatin, etoposide, paclitaxel and pemetrexed, 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. Radiation therapy uses high energy beams to kill tumor cells and shrink tumors. Giving atezolizumab with usual chemotherapy and radiation therapy may lower the chance of the tumor from growing or spreading.

PRIMARY OBJECTIVE:

I. To compare the pathologic complete response (pCR) by local review between participants randomized to conventional trimodality therapy, with or without atezolizumab.

SECONDARY OBJECTIVES:

I. To compare event-free survival (EFS) between the arms. II. To compare overall survival (OS) between the arms. III. To compare surgical resection rate and complete resection (R0) rate between the arms.

IV. To evaluate progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 among participants who do not undergo surgical resection, by treatment arm.

V. To compare the frequency and severity of toxicities between the arms.

ADDITIONAL OBJECTIVES:

I. To bank blood and tissue for future research. II. To evaluate the association between major pathologic response (MPR), as defined by the International Association for the Study of Lung Cancer (IASLC), and survival outcomes (OS, PFS).

III. To evaluate the association between pCR by centralized review and survival outcomes (OS, PFS).

IV. Evaluate the changes in fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) metrics (e.g., standardized uptake value \[SUV\] maximum \[max\], SUVpeak, SUVmax tumor-to-liver, SUVpeak tumor-to-liver, metabolic tumor volume, total lesion glycolysis, etc.) in participants randomized to receive trimodality therapy alone or in combination with atezolizumab and to evaluate the association with pCR.

V. Evaluate the extent to which the changes in diffusion weighted imaging (DWI)-magnetic resonance imagining (MRI) metrics (e.g., mean apparent diffusion coefficient or apparent diffusion coefficient \[ADC\] for the primary tumor, etc.) are associated with pCR in participants randomized to receive trimodality therapy alone or in combination with atezolizumab.

VI. Evaluate the extent to which changes in computed tomography (CT) tumor volume, unidimensional lesion changes per RECIST 1.1 and bidimensional lesion changes per World Health Organization (WHO) criteria are associated with pCR in participants randomized to receive trimodality therapy alone or in combination with atezolizumab.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Patients also receive one of the chemotherapy combinations below depending on their previous therapy and disease. Between the first day of chemotherapy and the first day of cycle 2 of chemotherapy, patients undergo external beam radiation therapy 5 days per week. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 21 and 90 days after treatment, patients undergo surgery. Within 42 days after completion of surgery, patients then receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive one of the chemotherapy combinations below depending on their previous therapy and disease. Between the first day of chemotherapy and the first day of cycle 2 of chemotherapy, patients also undergo external beam radiation therapy 5 days per week. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning 21 and 90 days after treatment, patients undergo surgery.

Patients receive one of the chemotherapy combinations:

1. Cisplatin IV over 2 hours on day 1 and etoposide IV over 30-60 minutes on days 1-3.
2. Carboplatin IV over 60 minutes on day 1 and etoposide IV over 30-60 minutes on days 1-3.
3. Paclitaxel IV over 3 hours and carboplatin IV over 60 minutes on day 1.

   Patients with non-squamous NSCLC may receive one of the following combinations:
4. Pemetrexed IV over 10 minutes and carboplatin IV over 60 minutes on day 1.
5. Pemetrexed IV over 10 minutes and cisplatin IV over 2 hours on day 1.

Patients may undergo a PET scan, CT scan, and MRI on study. Patients also undergo tumor biopsies and blood sample collection throughout the trial.

Testing the Addition of an Immunotherapy Drug, Atezolizumab, to the Usual Chemotherapy Treatment During Radiation Therapy for Superior Sulcus Non-small Cell Lung Cancer

NASSIST (Neoadjuvant Chemoradiation +/- Immunotherapy Before Surgery for Superior Sulcus Tumors): A Randomized Phase II Trial of Trimodality +/- Atezolizumab in Resectable Superior Sulcus Non-Small Cell Lung Cancer

"NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."

Defined by the International Association for the Study of Lung Cancer, will be associated with and survival outcomes (OS, PFS).

Will be associated with survival outcomes (OS, PFS).

Changes in DWI-MRI metrics will be associated with pCR between arms.

Will assess unidimensional lesion changes per RECIST 1.1 and bidimensional lesion changes per World Health Organization (WHO) criteria. Will be associated with pCR in participants randomized to receive trimodality therapy alone or in combination with atezolizumab.

Defined as From date of Step1 Randomization to date of first documentation of progression that renders participant unable to receive planned protocol surgery, off protocol therapy for any reason without subsequent protocol surgery, relapse after surgery, symptomatic deterioration or death due to any reason, whichever comes first. The primary analysis of EFS will be done using a 1-sided 15% level log-rank test. Will be estimated using the method of Kaplan-Meier. 95% confidence intervals for the medians will be constructed using the method of Brookmeyer-Crowley. Fine-Gray method will be used for a competing risk analysis.

Will be estimated using the method of Kaplan-Meier. 95% confidence intervals for the medians will be constructed using the method of Brookmeyer-Crowley.

Will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be estimated using the method of Kaplan-Meier. 95% confidence intervals for the medians will be constructed using the method of Brookmeyer-Crowley.

Will compare the frequency and severity of toxicities between the arms.

National Cancer Institute (NCI)

Spots Global Cancer Trial Database for superior sulcus lung carcinoma