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

Lung Non-Small Cell Carcinoma Clinical Trial

Official title: 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

Status Withdrawn

Clinical Trial Summary

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.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Lung Non-Small Cell Carcinoma
• Stage IIB Lung Cancer AJCC v8
• Stage IIIA Lung Cancer AJCC v8

• NCT number: NCT04989283
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Withdrawn
• Phase: Phase 2
• Start date: September 9, 2021
• Completion date: May 10, 2031