Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers

NCT ID: NCT05063552

Last Updated: 2025-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

430 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-13

Study Completion Date

2027-12-15

Brief Summary

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This phase II/III compares the standard therapy (chemotherapy plus cetuximab) versus adding bevacizumab to standard chemotherapy, versus combination of just bevacizumab and atezolizumab in treating patients with head and neck cancer that has spread to other places in the body (metastatic or advanced stage) or has come back after prior treatment (recurrent). 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. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Cisplatin and carboplatin are in a class of chemotherapy medications known as platinum-containing compounds. They work by killing, stopping, or slowing the growth of cancer cells. Docetaxel is in a class of chemotherapy medications called taxanes. It stops cancer cells from growing and dividing and may kill them. The addition of bevacizumab to standard chemotherapy or combination therapy with bevacizumab and atezolizumab may be better than standard chemotherapy plus cetuximab in treating patients with recurrent/metastatic head and neck cancers.

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Detailed Description

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PRIMARY OBJECTIVES:

I. To evaluate progression-free survival (PFS) of patients treated with chemotherapy plus cetuximab, chemotherapy plus bevacizumab, and atezolizumab plus bevacizumab. (Phase II) II. To evaluate the overall survival (OS) of patients treated with chemotherapy plus cetuximab to the superior arm from the phase II portion of the protocol. (Phase III)

SECONDARY OBJECTIVES:

I. To evaluate the OS for the subset of patients with high PD-L1 expression, defined as combined positive score (CPS) \>= 20% on all arms of treatment.

II. To evaluate the toxicity of each arm of treatment.

IMAGING OBJECTIVES:

I. To establish the correlation between fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET) and computed tomography (CT) neck imaging biomarkers (maximum standard uptake value \[SUVmax\], metabolic tumor volume \[MTV\], total lesion glycolysis \[TLG\], tumor volume) and expression of PD-L1 expression (Low versus high, defined as CPS \< 20 versus CPS \>= 20).

II. To determine if 18FDG-PET/CT and CT neck imaging biomarkers at baseline will predict treatment response at nine to twelve weeks post the initiation of treatment, PFS, and OS.

EXPLORATORY OBJECTIVE:

I. To establish the correlation between 18F-FDG PET and CT neck radiomics features and PD-L1 expressions (Low versus high - defined as CPS \< 20 versus CPS \>= 20).

OUTLINE: This is a randomized phase II trial followed by a randomized phase III trial.

PHASE II: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or magnetic resonance imaging (MRI) throughout the trial. Patients may undergo echocardiography (ECHO) during screening.

ARM B: Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening.

ARM C: Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening.

PHASE III: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening.

ARM B: Patients receive treatment as in Arm B or C above based on results of the Phase II trial.

Patients undergo blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days and then every 3 months if patient is \< 2 years from randomization and every 6 months if patient is 2-5 years from randomization.

Conditions

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Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8 Metastatic Head and Neck Squamous Cell Carcinoma Metastatic Hypopharyngeal Squamous Cell Carcinoma Metastatic Laryngeal Squamous Cell Carcinoma Metastatic Lip and Oral Cavity Carcinoma Metastatic Nasal Cavity Squamous Cell Carcinoma Metastatic Nasopharyngeal Squamous Cell Carcinoma Metastatic Pharyngeal Squamous Cell Carcinoma Metastatic Sinonasal Squamous Cell Carcinoma Recurrent Head and Neck Squamous Cell Carcinoma Recurrent Hypopharyngeal Squamous Cell Carcinoma Recurrent Laryngeal Squamous Cell Carcinoma Recurrent Lip and Oral Cavity Squamous Cell Carcinoma Recurrent Nasopharyngeal Squamous Cell Carcinoma Recurrent Pharyngeal Squamous Cell Carcinoma Recurrent Sinonasal Squamous Cell Carcinoma Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8 Stage IV Hypopharyngeal Carcinoma AJCC v8 Stage IV Laryngeal Cancer AJCC v8 Stage IV Lip and Oral Cavity Cancer AJCC v8 Stage IV Nasopharyngeal Carcinoma AJCC v8 Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8 Stage IV Sinonasal Cancer AJCC v8

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase II, Arm A (Cetuximab, Docetaxel, Cisplatin, Carboplatin)

Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Carboplatin

Intervention Type DRUG

Given IV

Cetuximab

Intervention Type BIOLOGICAL

Given IV

Cisplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Docetaxel

Intervention Type DRUG

Given IV

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Phase II, Arm B(Docetaxel, Cisplatin/Carboplatin, Bevacizumab)

Patients receive bevacizumab IV over 30-90 minutes on day 1 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-60 minutes on day 1 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type BIOLOGICAL

Given IV

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Carboplatin

Intervention Type DRUG

Given IV

Cisplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Docetaxel

Intervention Type DRUG

Given IV

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Phase II, Arm C (Bevacizumab, Atezolizumab)

Patients receive bevacizumab IV over 30-90 minutes on day 1 and atezolizumab IV over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type BIOLOGICAL

Given IV

Bevacizumab

Intervention Type BIOLOGICAL

Given IV

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Phase III, Arm A (Cetuximab, Docetaxel, Cisplatin/Carboplatin)

Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 of each cycle, docetaxel IV over 1 hour on day 1 or days 1 and 8 of each cycle, and cisplatin IV or carboplatin IV on day 1 or days 1 and 8 of each cycle. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 or days 1 and 15 of each cycle of maintenance therapy. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan, a PET scan, and/or MRI throughout the trial. Patients may undergo ECHO during screening. Patients undergo blood sample collection throughout the study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Carboplatin

Intervention Type DRUG

Given IV

Cetuximab

Intervention Type BIOLOGICAL

Given IV

Cisplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Docetaxel

Intervention Type DRUG

Given IV

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Phase III, Arm B (Chemotherapy, Bevacizumab, Atezolizumab)

Patients receive treatment as in Arm B or C above based on results of the Phase II trial.

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type BIOLOGICAL

Given IV

Bevacizumab

Intervention Type BIOLOGICAL

Given IV

Carboplatin

Intervention Type DRUG

Given IV

Cisplatin

Intervention Type DRUG

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT scan

Docetaxel

Intervention Type DRUG

Given IV

Echocardiography Test

Intervention Type PROCEDURE

Undergo ECHO

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET scan

Interventions

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Atezolizumab

Given IV

Intervention Type BIOLOGICAL

Bevacizumab

Given IV

Intervention Type BIOLOGICAL

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Carboplatin

Given IV

Intervention Type DRUG

Cetuximab

Given IV

Intervention Type BIOLOGICAL

Cisplatin

Given IV

Intervention Type DRUG

Computed Tomography

Undergo CT scan

Intervention Type PROCEDURE

Docetaxel

Given IV

Intervention Type DRUG

Echocardiography Test

Undergo ECHO

Intervention Type PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET scan

Intervention Type PROCEDURE

Other Intervention Names

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MPDL 3280A MPDL 328OA MPDL-3280A MPDL3280A MPDL328OA RG 7446 RG-7446 RG7446 RO 5541267 RO-5541267 RO5541267 Tecentriq ABP 215 ABP-215 ABP215 Alymsys Anti-VEGF Anti-VEGF Humanized Monoclonal Antibody Anti-VEGF Monoclonal Antibody SIBP04 Anti-VEGF rhuMAb Avastin Avzivi Aybintio BAT 1706 BAT-1706 BAT1706 BAT1706 Biosimilar Bevacizumab awwb Bevacizumab Biosimilar ABP 215 Bevacizumab Biosimilar BAT1706 Bevacizumab Biosimilar BEVZ92 Bevacizumab Biosimilar BI 695502 Bevacizumab Biosimilar CBT 124 Bevacizumab Biosimilar CT-P16 Bevacizumab Biosimilar FKB238 Bevacizumab Biosimilar GB-222 Bevacizumab Biosimilar HD204 Bevacizumab Biosimilar HLX04 Bevacizumab Biosimilar IBI305 Bevacizumab Biosimilar LY01008 Bevacizumab Biosimilar MB02 Bevacizumab Biosimilar MIL60 Bevacizumab Biosimilar Mvasi Bevacizumab Biosimilar MYL-1402O Bevacizumab Biosimilar QL 1101 Bevacizumab Biosimilar QL1101 Bevacizumab Biosimilar RPH-001 Bevacizumab Biosimilar SCT501 Bevacizumab Biosimilar Zirabev Bevacizumab-adcd Bevacizumab-awwb Bevacizumab-aybi Bevacizumab-bvzr Bevacizumab-equi Bevacizumab-maly Bevacizumab-onbe Bevacizumab-tnjn BP102 BP102 Biosimilar CT P16 CT-P16 CTP16 Equidacent FKB 238 FKB-238 FKB238 HD204 Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer MB 02 MB-02 MB02 Mvasi MYL-1402O Onbevzi Oyavas PF 06439535 PF-06439535 PF06439535 QL1101 Recombinant Humanized Anti-VEGF Monoclonal Antibody rhuMab-VEGF SCT501 SIBP 04 SIBP-04 SIBP04 Vegzelma Zirabev Biological Sample Collection Biospecimen Collected Specimen Collection Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 JM8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo C 225 C-225 C225 Cetuximab Biosimilar CDP-1 Cetuximab Biosimilar CMAB009 Cetuximab Biosimilar KL 140 Chimeric Anti-EGFR Monoclonal Antibody Chimeric MoAb C225 Chimeric Monoclonal Antibody C225 Erbitux IMC-C225 Abiplatin Blastolem Briplatin CDDP Cis-diammine-dichloroplatinum Cis-diamminedichloridoplatinum Cis-diamminedichloro Platinum (II) Cis-diamminedichloroplatinum Cis-dichloroammine Platinum (II) Cis-platinous Diamine Dichloride Cis-platinum Cis-platinum II Cis-platinum II Diamine Dichloride Cismaplat Cisplatina Cisplatinum Cisplatyl Citoplatino Citosin Cysplatyna DDP Lederplatin Metaplatin Neoplatin Peyrone's Chloride Peyrone's Salt Placis Plastistil Platamine Platiblastin Platiblastin-S Platinex Platinol Platinol- AQ Platinol-AQ Platinol-AQ VHA Plus Platinoxan Platinum Platinum Diamminodichloride Platiran Platistin Platosin CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography Docecad RP 56976 RP-56976 RP56976 Taxotere Taxotere Injection Concentrate EC Echocardiography Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT

Eligibility Criteria

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Inclusion Criteria

* Patient must have histologically confirmed squamous cell carcinoma of the head and neck (HNSCC) (excluding squamous cell carcinoma \[SCC\] of salivary glands, Epstein-Barr virus \[EBV\]-associated nasopharynx and skin)
* Patient must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Measurements must be obtained within 4 weeks prior to randomization
* Patient must be \>= 18 years of age
* Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
* Patient must have disease progression after prior therapy with an immune checkpoint inhibitor (ICI) in the first-line setting for recurrent/metastatic disease. Patient must have received first-line immune checkpoint inhibition for at least 6 weeks. Patients who have recurred or progressed within 12 weeks of immune checkpoint inhibition administered in the definitive setting for locally advanced disease (for e.g., in the context of a clinical trial) will also be eligible if local therapies are not feasible
* Prior combination immunotherapies are permitted, but patient must not have had prior antiangiogenic treatment (e.g., bevacizumab, ziv-aflibercept, ramucirumab, sorafenib, sunitinib, pazopanib, regorafenib, lenvatinib, etc.). Patient must have completed any prior investigational therapy at least 28 days prior to randomization.

* NOTE: Patients who received platinum/taxanes in the locally-advanced or recurrent/metastatic setting and did not progress for at least 4 months thereafter, will be eligible for this study. Patients who received cetuximab in the locally-advanced setting and did not progress for at least 4 months thereafter, will also be eligible for this study
* Patient must not have a history of \>= grade 3 immune-related adverse event on prior ICI therapy (except those that could be managed with steroids \[e.g., dermatologic toxicity, asymptomatic elevation of pancreatic enzymes, etc.\]) and ICI could eventually be resumed. Patients who developed grade 3 endocrinopathies but are now stable on hormone supplementation and/or a daily prednisone dose of =\< 10 mg (or equivalent doses of another glucocorticoid), will be permitted on this trial
* Patient must not have a history of PD-1 inhibitor-induced hyper-progression, defined as 100% increase in tumor burden within 8 weeks (or 50% within 4 weeks) of initiating ICI and associated with clinical deterioration
* Patient must not have any of the following criteria due to the possibility of increased risk for tumor bleeding with bevacizumab therapy:

* Prior carotid bleeding,
* Tumors that invade major vessels (e.g., the carotid) as shown unequivocally by imaging studies,
* Central (e.g., within 2 cm from the hilum) lung metastases that are cavitary as shown unequivocally by imaging studies,
* Any prior history of bleeding related to the current head and neck cancer,
* History of gross hemoptysis (bright red blood of 1/2 teaspoon or more per episode of coughing) within 3 months prior to randomization
* Patient must not have uncontrolled hypertension, a history of hypertensive crisis or hypertensive encephalopathy, or a history of grade 4 thromboembolism
* Patient must not have a history of coagulopathy or hemorrhagic disorders
* Patient must not have a history of thrombosis (e.g., pulmonary embolism or deep venous thrombosis) currently requiring therapeutic anticoagulation (prophylactic use of anticoagulation is allowed)
* Patient must not be receiving chronic daily treatment with aspirin (\> 325 mg/day) or non-steroidal anti-inflammatory agents (NSAID's) known to inhibit platelet function. The use of anti-platelet agents \[e.g., dipyridamole (Persatine), ticlopidine (Ticlid), clopidogrel (Plavix)\] is allowed only if patient is not receiving concurrent aspirin or NSAID's known to inhibit platelet function
* Patient must have PD-L1 expression \>= 1% by CPS in the tumor and/or immune cells

* NOTE: Enrolling centers should test for PD-L1 CPS preferably using the SP263 assay. Where this is not feasible, using their preferred Clinical Laboratory Improvement Act (CLIA)-certified or similar assay will be accepted. It is preferred for standard of care (SOC) PD-L1 assessments to be done on post-first line ICI samples if available, but SOC PD-L1 assessments on pre-ICI samples will be accepted for eligibility
* Patient must not have a severe infection within 4 weeks prior to randomization, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. Patients must not have active tuberculosis
* Patient must not have a history of non-infectious pneumonitis requiring steroids at doses greater than or equal to 10 mg per day of prednisone or the equivalent on first line immunotherapy
* Patient must not have a history of solid organ transplantation or stem-cell transplant
* Patient must not be on immunosuppressive medication within 7 days prior to randomization except for: intranasal, inhaled, or topical steroids, local steroid injection, systemic corticosteroids at doses less than or equal to 10 mg per day of prednisone or the equivalent, or steroids used as premedication for hypersensitivity reactions
* Patient must not have an active autoimmune disease that requires systemic treatment within 2 years prior to randomization. Patients who are receiving replacement therapy for adrenal or pituitary insufficiency will not be excluded
* Patient must not have had a severe hypersensitivity reaction to any of the drug components used on this protocol or to chimeric or humanized antibodies or fusion proteins
* Patient must not have received any live vaccine within 30 days prior to randomization and while participating in the study (and continue for 5 months after the last dose of atezolizumab on Arm C). Live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and coronavirus disease 2019 (COVID-19) (Note: intranasal influenza vaccines, such as Flu-Mist \[registered trademark\] are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events
* Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used.

* All patients of childbearing potential must have a blood test or urine study within 14 days prior to randomization to rule out pregnancy.
* A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
* Patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for the duration of their participation in the study and for 2 months after the last dose of treatment for patients assigned to Arm A and for 6 months after the last dose of protocol treatment for patients assigned to Arms B or C.

* NOTE: Patients must also not breastfeed while on treatment and for 2 months after the last dose of treatment for patients assigned to Arm A and for 6 months after the last dose of treatment for patients assigned to Arms B or C
* Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
* Leukocytes \>= 3,000/mcL (must be obtained =\< 14 days prior to protocol randomization)
* Absolute neutrophil count (ANC) \>= 1,500/mcL (must be obtained =\< 14 days prior to protocol randomization)
* Platelets \>= 100,000/mcL (must be obtained =\< 14 days prior to protocol randomization)
* Hemoglobin (Hgb) \> 9 g/dL (must be obtained =\< 14 days prior to protocol randomization) (Note: Patient may be transfused to meet this criteria)
* Total bilirubin =\< 2.0 x institutional upper limit of normal (ULN) (=\< 5.0 x institutional ULN if hepatic metastases present or =\< 3 x ULN for patients with known Gilbert's disease) (must be obtained =\< 14 days prior to protocol randomization)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN (\< 5.0 x institutional ULN if hepatic metastases present) (must be obtained =\< 14 days prior to protocol randomization)
* Alkaline phosphatase \< 2.5 x institutional ULN (\< 5.0 x institutional ULN if hepatic or bone metastases present) (must be obtained =\< 14 days prior to protocol randomization)
* Creatinine =\< 1.5 x institutional ULN (must be obtained =\< 14 days prior to protocol randomization)
* Patients with uncontrolled or symptomatic hypercalcemia (ionized calcium \> 1.5 mmol/L, calcium \> 12 mg/dL or corrected serum calcium \> ULN) must have their calcium levels corrected prior to randomization
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of randomization are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Patients must not have untreated brain metastases or leptomeningeal disease
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients must not have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients may have indwelling catheters (e.g., PleurX \[registered trademark\])
* Patient must not have significant cardiovascular disease (such as New York Heart Association class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to randomization, or unstable arrhythmia or unstable angina at the time of randomization
* Patient must not receive any other chemotherapy, immunotherapy, antitumor hormonal therapy (excluding contraceptives and replacement steroids), radiation therapy, or experimental medications while on protocol treatment. Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization and patients must be recovered from the effects of radiation (there is no required minimum recovery period
* Patient must not have had a surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to randomization, or anticipation of need for major surgical procedure while on protocol treatment
* Patient must not have any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of the agents used in this protocol, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
* Patient must not have a history of abdominal fistula, gastrointestinal (GI) perforation, intra-abdominal abscess, or active GI bleeding within 6 months prior to randomization
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aarti Bhatia

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

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UPMC Memorial

York, Pennsylvania, United States

Site Status

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Epic Care-Dublin

Dublin, California, United States

Site Status

Epic Care Partners in Cancer Care

Emeryville, California, United States

Site Status

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, United States

Site Status

Contra Costa Regional Medical Center

Martinez, California, United States

Site Status

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status

VA Palo Alto Health Care System

Palo Alto, California, United States

Site Status

Smilow Cancer Hospital-Derby Care Center

Derby, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center-Fairfield

Fairfield, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center at Glastonbury

Glastonbury, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, United States

Site Status

Smilow Cancer Hospital-Orange Care Center

Orange, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center at Long Ridge

Stamford, Connecticut, United States

Site Status

Smilow Cancer Hospital-Torrington Care Center

Torrington, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States

Site Status

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, United States

Site Status

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, United States

Site Status

Helen F Graham Cancer Center

Newark, Delaware, United States

Site Status

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

Site Status

MedStar Washington Hospital Center

Washington D.C., District of Columbia, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Site Status

Broward Health Medical Center

Fort Lauderdale, Florida, United States

Site Status

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States

Site Status

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Site Status

Emory University Hospital Midtown

Atlanta, Georgia, United States

Site Status

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

Hawaii Cancer Care Inc - Waterfront Plaza

Honolulu, Hawaii, United States

Site Status

Queen's Cancer Cenrer - POB I

Honolulu, Hawaii, United States

Site Status

Queen's Medical Center

Honolulu, Hawaii, United States

Site Status

Queen's Cancer Center - Kuakini

Honolulu, Hawaii, United States

Site Status

Hawaii Cancer Care - Westridge

‘Aiea, Hawaii, United States

Site Status

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Site Status

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Fruitland

Fruitland, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Meridian

Meridian, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Nampa

Nampa, Idaho, United States

Site Status

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, United States

Site Status

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho, United States

Site Status

Saint Luke's Cancer Institute - Twin Falls

Twin Falls, Idaho, United States

Site Status

Rush-Copley Medical Center

Aurora, Illinois, United States

Site Status

Centralia Oncology Clinic

Centralia, Illinois, United States

Site Status

John H Stroger Jr Hospital of Cook County

Chicago, Illinois, United States

Site Status

University of Illinois

Chicago, Illinois, United States

Site Status

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status

Carle at The Riverfront

Danville, Illinois, United States

Site Status

Cancer Care Specialists of Illinois - Decatur

Decatur, Illinois, United States

Site Status

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status

Carle Physician Group-Effingham

Effingham, Illinois, United States

Site Status

Crossroads Cancer Center

Effingham, Illinois, United States

Site Status

Ingalls Memorial Hospital

Harvey, Illinois, United States

Site Status

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, United States

Site Status

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, United States

Site Status

Cancer Care Center of O'Fallon

O'Fallon, Illinois, United States

Site Status

HSHS Saint Elizabeth's Hospital

O'Fallon, Illinois, United States

Site Status

University of Chicago Medicine-Orland Park

Orland Park, Illinois, United States

Site Status

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Site Status

Springfield Clinic

Springfield, Illinois, United States

Site Status

Springfield Memorial Hospital

Springfield, Illinois, United States

Site Status

Carle Cancer Center

Urbana, Illinois, United States

Site Status

Rush-Copley Healthcare Center

Yorkville, Illinois, United States

Site Status

Mary Greeley Medical Center

Ames, Iowa, United States

Site Status

McFarland Clinic - Ames

Ames, Iowa, United States

Site Status

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, United States

Site Status

McFarland Clinic - Boone

Boone, Iowa, United States

Site Status

Mercy Cancer Center-West Lakes

Clive, Iowa, United States

Site Status

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa, United States

Site Status

Greater Regional Medical Center

Creston, Iowa, United States

Site Status

Iowa Methodist Medical Center

Des Moines, Iowa, United States

Site Status

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, United States

Site Status

Mercy Medical Center - Des Moines

Des Moines, Iowa, United States

Site Status

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa, United States

Site Status

McFarland Clinic - Trinity Cancer Center

Fort Dodge, Iowa, United States

Site Status

McFarland Clinic - Jefferson

Jefferson, Iowa, United States

Site Status

McFarland Clinic - Marshalltown

Marshalltown, Iowa, United States

Site Status

UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa, United States

Site Status

Mercy Medical Center-West Lakes

West Des Moines, Iowa, United States

Site Status

University Medical Center New Orleans

New Orleans, Louisiana, United States

Site Status

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Site Status

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status

UPMC Western Maryland

Cumberland, Maryland, United States

Site Status

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, United States

Site Status

Mercy Hospital

Coon Rapids, Minnesota, United States

Site Status

Abbott-Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

Park Nicollet Clinic - Saint Louis Park

Saint Louis Park, Minnesota, United States

Site Status

Regions Hospital

Saint Paul, Minnesota, United States

Site Status

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Site Status

Mercy Hospital South

St Louis, Missouri, United States

Site Status

Community Hospital of Anaconda

Anaconda, Montana, United States

Site Status

Billings Clinic Cancer Center

Billings, Montana, United States

Site Status

Bozeman Health Deaconess Hospital

Bozeman, Montana, United States

Site Status

Benefis Sletten Cancer Institute

Great Falls, Montana, United States

Site Status

Community Medical Center

Missoula, Montana, United States

Site Status

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

Memorial Medical Center-Las Cruces

Las Cruces, New Mexico, United States

Site Status

Southeastern Medical Oncology Center-Clinton

Clinton, North Carolina, United States

Site Status

Southeastern Medical Oncology Center-Goldsboro

Goldsboro, North Carolina, United States

Site Status

Southeastern Medical Oncology Center-Jacksonville

Jacksonville, North Carolina, United States

Site Status

Miami Valley Hospital South

Centerville, Ohio, United States

Site Status

Miami Valley Hospital

Dayton, Ohio, United States

Site Status

Premier Blood and Cancer Center

Dayton, Ohio, United States

Site Status

Dayton Physician LLC - Englewood

Dayton, Ohio, United States

Site Status

Miami Valley Hospital North

Dayton, Ohio, United States

Site Status

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio, United States

Site Status

Miami Valley Cancer Care and Infusion

Greenville, Ohio, United States

Site Status

Kettering Medical Center

Kettering, Ohio, United States

Site Status

Trinity's Tony Teramana Cancer Center

Steubenville, Ohio, United States

Site Status

Toledo Clinic Cancer Centers-Toledo

Toledo, Ohio, United States

Site Status

Upper Valley Medical Center

Troy, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Providence Cancer Institute Clackamas Clinic

Clackamas, Oregon, United States

Site Status

Providence Newberg Medical Center

Newberg, Oregon, United States

Site Status

Providence Portland Medical Center

Portland, Oregon, United States

Site Status

Providence Saint Vincent Medical Center

Portland, Oregon, United States

Site Status

UPMC Altoona

Altoona, Pennsylvania, United States

Site Status

UPMC-Heritage Valley Health System Beaver

Beaver, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center at Butler Health System

Butler, Pennsylvania, United States

Site Status

UPMC Camp Hill

Camp Hill, Pennsylvania, United States

Site Status

Carlisle Regional Cancer Center

Carlisle, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center - Passavant - Cranberry

Cranberry Township, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center Erie

Erie, Pennsylvania, United States

Site Status

UPMC Cancer Center at UPMC Horizon

Farrell, Pennsylvania, United States

Site Status

UPMC Cancer Centers - Arnold Palmer Pavilion

Greensburg, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center in Greenville/UPMC Horizon

Greenville, Pennsylvania, United States

Site Status

UPMC Pinnacle Cancer Center/Community Osteopathic Campus

Harrisburg, Pennsylvania, United States

Site Status

IRMC Cancer Center

Indiana, Pennsylvania, United States

Site Status

UPMC-Johnstown/John P. Murtha Regional Cancer Center

Johnstown, Pennsylvania, United States

Site Status

UPMC Cancer Center at UPMC McKeesport

McKeesport, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion

Mechanicsburg, Pennsylvania, United States

Site Status

Forbes Hospital

Monroeville, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center - Monroeville

Monroeville, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center in Coraopolis

Moon Township, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center - Part of Frick Hospital

Mount Pleasant, Pennsylvania, United States

Site Status

Arnold Palmer Cancer Center Medical Oncology Norwin

N. Huntingdon, Pennsylvania, United States

Site Status

UPMC Cancer Center-Natrona Heights

Natrona Heights, Pennsylvania, United States

Site Status

UPMC Hillman Cancer Center - New Castle

New Castle, Pennsylvania, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Jefferson Torresdale Hospital

Philadelphia, Pennsylvania, United States

Site Status

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC-Saint Margaret

Pittsburgh, Pennsylvania, United States

Site Status

UPMC-Mercy Hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status

UPMC-Passavant Hospital

Pittsburgh, Pennsylvania, United States

Site Status

UPMC-Saint Clair Hospital Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

UPMC Cancer Center at UPMC Northwest

Seneca, Pennsylvania, United States

Site Status

UPMC Cancer Center-Uniontown

Uniontown, Pennsylvania, United States

Site Status

UPMC Cancer Center-Washington

Washington, Pennsylvania, United States

Site Status

UPMC West Mifflin-Cancer Center Jefferson

West Mifflin, Pennsylvania, United States

Site Status

Divine Providence Hospital

Williamsport, Pennsylvania, United States

Site Status

Asplundh Cancer Pavilion

Willow Grove, Pennsylvania, United States

Site Status

Smilow Cancer Hospital Care Center - Westerly

Westerly, Rhode Island, United States

Site Status

Rapid City Regional Hospital

Rapid City, South Dakota, United States

Site Status

Thompson Cancer Survival Center

Knoxville, Tennessee, United States

Site Status

Thompson Cancer Survival Center - West

Knoxville, Tennessee, United States

Site Status

Thompson Oncology Group-Lenoir City

Lenoir City, Tennessee, United States

Site Status

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Thompson Oncology Group-Oak Ridge

Oak Ridge, Tennessee, United States

Site Status

Dartmouth Cancer Center - North

Saint Johnsbury, Vermont, United States

Site Status

West Virginia University Charleston Division

Charleston, West Virginia, United States

Site Status

ProHealth D N Greenwald Center

Mukwonago, Wisconsin, United States

Site Status

ProHealth Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, United States

Site Status

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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NCI-2021-10021

Identifier Type: REGISTRY

Identifier Source: secondary_id

EA3202

Identifier Type: OTHER

Identifier Source: secondary_id

EA3202

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180820

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2021-10021

Identifier Type: -

Identifier Source: org_study_id

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