Clinical trial NCT04989283: Testing the Addition of an Immunotherapy Drug, Atezolizumab, to the Usual Chemotherapy Treatment During Radiation Therapy for Superior Sulcus Non-small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Lung Non-Small Cell Carcinoma
Stage IIB Lung Cancer AJCC v8
Stage IIIA Lung Cancer AJCC v8
Superior Sulcus Lung Carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2021-08-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* STEP 1 RANDOMIZATION: Participants must have histologically confirmed cT3/T4, N0/1, M0 non-small cell lung cancer (NSCLC) of the superior sulcus arising in the apex of the lung, involving apical chest wall structures (parietal pleura and beyond) above the level of the second rib
* STEP 1 RANDOMIZATION: Participants must have eligibility affirmed by a thoracic surgeon, medical oncologist and radiation oncologist. Participant must be a candidate for surgical resection and chemoradiation therapy. The site treating investigator must sign off to indicate that eligibility has been affirmed by each specialist
* STEP 1 RANDOMIZATION: Participants may have measurable or non-measurable disease. Measurable disease must be assessed within 28 days prior to Step 1 Randomization. Non-measurable disease must be assessed within 42 days prior to Step 1 Randomization. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form
* STEP 1 RANDOMIZATION: Participants must have an MRI or CT scan of the brain (with contrast highly recommend) within 42 days prior to Step 1 Randomization
* STEP 1 RANDOMIZATION: Participants must have a CT (chest with contrast highly recommended), contrast MRI (thoracic inlet), and FDG-PET/CT performed within 28 days prior to Step 1 Randomization

  * Note: DWI (Diffusion weighting imaging) is highly recommended on the MRI
* STEP 1 RANDOMIZATION: Participants may participate in concomitant non-therapeutic trials (e.g., palliative care assessment or quality of life studies)
* STEP 1 RANDOMIZATION: History and physical exam must be obtained within 28 days of Step 1 Randomization
* STEP 1 RANDOMIZATION: Participants must have Zubrod performance status of 0-1 documented within 28 days prior to Step 1 Randomization
* STEP 1 RANDOMIZATION: Participants must be \>= 18 years old
* STEP 1 RANDOMIZATION: Leukocytes \>= 3,000/uL (within 28 days prior to Step 1 Randomization)
* STEP 1 RANDOMIZATION: Absolute neutrophil count \>= 1,500/uL (within 28 days prior to Step 1 Randomization)
* STEP 1 RANDOMIZATION: Platelets \>= 100,000/uL (within 28 days prior to Step 1 Randomization)
* STEP 1 RANDOMIZATION: Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to Step 1 Randomization)
* STEP 1 RANDOMIZATION: Participants with known Gilbert disease: total bilirubin =\< 3 x (ULN) (within 28 days prior to Step 1 Randomization)
* STEP 1 RANDOMIZATION: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x institutional ULN (within 28 days prior to Step 1 Randomization)
* STEP 1 RANDOMIZATION: Hemoglobin \>= 9 g/dL (within 28 days prior to Step 1 Randomization)
* STEP 1 RANDOMIZATION: Participants must not have higher than grade 2 hypercalcemia prior to Step I Randomization
* STEP 1 RANDOMIZATION: Participants must have a serum creatinine =\< the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance \>= 50 mL/min using the following Cockcroft-Gault formula. This specimen must have been drawn and processed within 28 days prior to Step 1 Randomization
* STEP 1 RANDOMIZATION: Participants with known human immunodeficiency virus (HIV)-infection must be receiving anti-retroviral therapy and have undetectable viral load test within 6 months prior to Step 1 Randomization
* STEP 1 RANDOMIZATION: Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load on suppressive therapy within 28 days prior to Step 1 Randomization
* STEP 1 RANDOMIZATION: Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with HCV infection who are currently on treatment must have an undetectable HCV viral load within in 28 days prior to Step 1 Randomization
* STEP 1 RANDOMIZATION: Participants of reproductive potential must have a negative serum pregnancy test within 14 days prior to Step 1 Randomization
* STEP 1 RANDOMIZATION: Participants must be offered the opportunity to participate in specimen banking
* STEP 1 RANDOMIZATION: Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines. For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations
* STEP 2 SURGERY: Participants must have a CT scan of the chest with contrast, FDG-PET/CT scan and MRI scan of the thoracic inlet (with intravenous contrast and DWI highly recommended) within 28 days prior to Step 2 Registration
* STEP 2 SURGERY: Participants must be evaluated for appropriateness of surgery by a thoracic surgeon within 6 weeks after completion of neoadjuvant therapy prior to Step 2 Registration
* STEP 2 SURGERY: Participant's surgery must occur between 21 and 90 days following the end of participant's final cycle of chemotherapy +/- atezolizumab
* STEP 2 SURGERY: Participants must have received at least two cycles of all assigned protocol drugs during neoadjuvant protocol treatment and must have received at least 45 GY RT of the planned 61.2 GY RT during neoadjuvant protocol treatment
* STEP 2 SURGERY: Participants must have a Zubrod Performance Status of 0-1 documented within 28 days prior to Step 2 Registration
* STEP 2 SURGERY: Participants must have postoperative predicted forced expiratory volume in 1 second (FEV1) \> 35% and postoperative predicted diffusion capacity of the lung for carbon monoxide (DLCO) \> 35%. Pulmonary function tests to ascertain these values must be obtained within 28 days prior to Step 2 Registration
* STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Participants must have received surgical resection of the lung cancer and side effects must have recovered to =\< grade 2 within 42 days after surgery and prior to Step 3 Registration
* STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Participants must have a Zubrod Performance Status of 0-1 documented within 28 days prior to Step 3 Registration
* STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Leukocytes \>= 3,000/uL (within 28 days prior to Step 3 Registration)
* STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Absolute neutrophil count \>= 1,000/uL (within 28 days prior to Step 3 Registration)
* STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Platelets \>= 100,000/uL (within 28 days prior to Step 3 Registration)
* STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Hemoglobin \>= 9 g/dL (within 28 days prior to Step 3 Registration)
* STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Total bilirubin =\< institutional upper limit of normal (ULN) (within 28 days prior to Step 3 Registration)
* STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): AST and ALT =\< 3 x institutional ULN (within 28 days prior to Step 3 Registration)
* STEP 3 MAINTENANCE THERAPY (ARM 1 ONLY): Participants must have adequate kidney function defined as creatinine =\< 1.5 x ULN documented within 28 days prior to Step 3 Registration

Exclusion Criteria:

* STEP 1 RANDOMIZATION: Participants must not have had prior therapy for this cancer including surgery, chemotherapy, immunotherapy, targeted therapy agent, and/or radiation therapy
* STEP 1 RANDOMIZATION: Participants must not have undergone prior radiation to overlapping regions of planned protocol radiation therapy (RT) treatment area
* STEP 1 RANDOMIZATION: Participants must not have had prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* STEP 1 RANDOMIZATION: Participants must not have had prior treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks prior to Step 1 Randomization
* STEP 1 RANDOMIZATION: Participants must not have a known allergy or hypersensitivity to any component of the carboplatin, pemetrexed, cisplatin, etoposide and paclitaxel formulation
* STEP 1 RANDOMIZATION: Participants must not have any grade III/IV cardiac disease as defined by the New York Heart Association Criteria (i.e., participants with cardiac disease resulting in marked limitation of physical activity or resulting in inability to carry on any physical activity without discomfort), unstable angina pectoris, and myocardial infarction within 3 months, or serious uncontrolled cardiac arrhythmia
* STEP 1 RANDOMIZATION: Participants must not have known active tuberculosis (TB)
* STEP 1 RANDOMIZATION: Participants must not have uncontrolled non-malignant pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (more than once a month). Note: Participants with indwelling catheters (e.g., PleurX \[registered trademark\]) are allowed
* STEP 1 RANDOMIZATION: Patients must not have undergone prior allogeneic stem cell transplantation or prior solid organ transplantation
* STEP 1 RANDOMIZATION: Participants must NOT have a history of severe allergic, anaphylactic, or other known hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
* STEP 1 RANDOMIZATION: Participants must NOT have a known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
* STEP 1 RANDOMIZATION: Participants must not have severe or active infections within 28 days prior to Step 1 Randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
* STEP 1 RANDOMIZATION: Participants must not have active autoimmune disease requiring therapy within the past 6 months. Participants must not have active autoimmune disease that has required systemic treatment within the past two years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Autoimmune diseases include, but are not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. This protocol includes an immunotherapy agent which can precipitate known autoimmune diseases
* STEP 1 RANDOMIZATION: Participants must not have history of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (e.g., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis. This protocol includes an immunotherapy agent which can precipitate known pneumonitis
* STEP 1 RANDOMIZATION: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
* STEP 1 RANDOMIZATION: Participants must not have received a live attenuated vaccination within 28 days prior to Step 1 Randomization. All coronavirus disease 2019 (COVID-19) vaccines that have received Food and Drug Administration (FDA) approval or FDA emergency use authorization are acceptable
* STEP 1 RANDOMIZATION: Participants must not have had a major surgery within 14 days prior to Step 1 Randomization. Participants must have fully recovered from the effects of prior surgery in the opinion of the treating investigator
* STEP 1 RANDOMIZATION: Participants must not be pregnant or nursing due to carcinogenic and teratogenic effects of treatment. Women/men of reproductive potential must have agreed to use an effective contraceptive method while on study treatment and for 5 months after the last dose. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate participant chooses to become heterosexually active during the time period for use of contraceptive measures outlined, he/she is responsible for beginning contraceptive measures

Primary outcomes:
measure: Pathologic complete response (pCR) by local review
timeFrame: Up to 6 years
Secondary outcomes:
measure: Event-free survival (EFS)
timeFrame: Up to 6 years
measure: Overall survival (OS)
timeFrame: From date of Step 1 Randomization to date of death due to any cause, assessed up to 6 years
measure: Surgical resection rate
timeFrame: Up to 6 years
measure: Complete resection (R0) rate
timeFrame: Up to 6 years
measure: Progression-free survival (PFS)
timeFrame: From date of Step 1 Randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever comes first, assessed up to 6 years
measure: Incidence of adverse events
timeFrame: Up to 6 years
Other outcomes:
measure: Bank blood and tissue for future research
timeFrame: Up to 6 years
measure: Major pathologic response
timeFrame: Up to 6 years
measure: pCR by centralized review
timeFrame: Up to 6 years
measure: Changes in fludeoxyglucose F-18-positron emission tomography metrics
timeFrame: Baseline up to 6 years
measure: Changes in diffusion weighted imaging (DWI)-magnetic resonance imagining (MRI) metrics
timeFrame: Baseline up to 6 years
measure: Changes in computed tomography tumor volume
timeFrame: Baseline up to 6 years
Locations:
city: Jonesboro
country: United States
facility: NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
state: Arkansas
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boise
country: United States
facility: Saint Alphonsus Cancer Care Center-Boise
state: Idaho
city: Caldwell
country: United States
facility: Saint Alphonsus Cancer Care Center-Caldwell
state: Idaho
city: Coeur d'Alene
country: United States
facility: Kootenai Health - Coeur d'Alene
state: Idaho
city: Nampa
country: United States
facility: Saint Alphonsus Cancer Care Center-Nampa
state: Idaho
city: Post Falls
country: United States
facility: Kootenai Clinic Cancer Services - Post Falls
state: Idaho
city: Sandpoint
country: United States
facility: Kootenai Cancer Clinic
state: Idaho
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Danville
country: United States
facility: Carle at The Riverfront
state: Illinois
city: Effingham
country: United States
facility: Carle Physician Group-Effingham
state: Illinois
city: Mattoon
country: United States
facility: Carle Physician Group-Mattoon/Charleston
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Ames
country: United States
facility: Mary Greeley Medical Center
state: Iowa
city: Ames
country: United States
facility: McFarland Clinic - Ames
state: Iowa
city: Boone
country: United States
facility: McFarland Clinic - Boone
state: Iowa
city: Fort Dodge
country: United States
facility: McFarland Clinic - Trinity Cancer Center
state: Iowa
city: Jefferson
country: United States
facility: McFarland Clinic - Jefferson
state: Iowa
city: Marshalltown
country: United States
facility: McFarland Clinic - Marshalltown
state: Iowa
city: Columbus
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Golden Triangle
state: Mississippi
city: Grenada
country: United States
facility: Baptist Cancer Center-Grenada
state: Mississippi
city: New Albany
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Union County
state: Mississippi
city: Oxford
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Oxford
state: Mississippi
city: Southhaven
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Desoto
state: Mississippi
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Great Falls
country: United States
facility: Benefis Healthcare- Sletten Cancer Institute
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Hospital
state: Montana
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
state: New Hampshire
city: New York
country: United States
facility: Mount Sinai Chelsea
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Chillicothe
country: United States
facility: Adena Regional Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center-UC Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Mark H Zangmeister Center
state: Ohio
city: West Chester
country: United States
facility: University of Cincinnati Cancer Center-West Chester
state: Ohio
city: Westerville
country: United States
facility: Saint Ann's Hospital
state: Ohio
city: Zanesville
country: United States
facility: Genesis Healthcare System Cancer Care Center
state: Ohio
city: Lawton
country: United States
facility: Cancer Centers of Southwest Oklahoma Research
state: Oklahoma
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Ontario
country: United States
facility: Saint Alphonsus Medical Center-Ontario
state: Oregon
city: Collierville
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Collierville
state: Tennessee
city: Memphis
country: United States
facility: Baptist Memorial Hospital and Cancer Center-Memphis
state: Tennessee
city: Saint Johnsbury
country: United States
facility: Norris Cotton Cancer Center-North
state: Vermont
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic-Minocqua Center
state: Wisconsin
Study officials:
affiliation: SWOG Cancer Research Network
name: Raymond U Osarogiagbon
role: PRINCIPAL_INVESTIGATOR
References: