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Clinical Trial Summary

This phase II/III compares the standard chemotherapy alone to adding bevacizumab to standard chemotherapy, or a combination of just bevacizumab and atezolizumab in treating patients with head and neck cancers that have spread to other places in the body (advanced stage). 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 and cetuximab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as cisplatin, carboplatin, and docetaxel, 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. The addition of bevacizumab and/or atezolizumab could shrink or stabilize head and neck cancers or stop them from growing.


Clinical Trial Description

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-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 30-60 minutes on days 1, 8, and 15, docetaxel IV over 1 hour on day 1, and cisplatin IV or carboplatin IV on day 1. 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 30-60 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive bevacizumab IV over 30-90 on day 1, docetaxel IV over 1 hour on day 1, and cisplatin IV or carboplatin IV on day 1. 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. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive bevacizumab IV over 30-90 on day 1 and atezolizumab over 30-60 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. PHASE III: Patients are randomized to 1 of 2 arms. ARM A: Patients receive cetuximab IV over 30-60 minutes on days 1, 8, and 15, docetaxel IV over 1 hour on day 1, and cisplatin IV or carboplatin IV on day 1. 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 30-60 minutes on day 1. Cycles repeat every 21 days for 2 years in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive treatment as in Arm B or C above based on results of the Phase II trial. 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. ;


Study Design


Related Conditions & MeSH terms

  • Carcinoma
  • Carcinoma, Squamous Cell
  • Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
  • Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
  • Head and Neck Neoplasms
  • Laryngeal Neoplasms
  • Lip Neoplasms
  • Metastatic Head and Neck Squamous Cell Carcinoma
  • Mouth Neoplasms
  • Nasopharyngeal Carcinoma
  • Oropharyngeal Neoplasms
  • Pathologic Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
  • 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 Pharyngeal Squamous Cell Carcinoma
  • Recurrent Sinonasal Squamous Cell Carcinoma
  • Squamous Cell Carcinoma of Head and Neck
  • 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 IVA Hypopharyngeal Carcinoma AJCC v8
  • Stage IVA Laryngeal Cancer AJCC v8
  • Stage IVA Lip and Oral Cavity Cancer AJCC v8
  • Stage IVA Nasopharyngeal Carcinoma AJCC v8
  • Stage IVA Oropharyngeal (p16-Negative) Carcinoma AJCC v8
  • Stage IVB Hypopharyngeal Carcinoma AJCC v8
  • Stage IVB Laryngeal Cancer AJCC v8
  • Stage IVB Lip and Oral Cavity Cancer AJCC v8
  • Stage IVB Nasopharyngeal Carcinoma AJCC v8
  • Stage IVB Oropharyngeal (p16-Negative) Carcinoma AJCC v8
  • Stage IVC Hypopharyngeal Carcinoma AJCC v8
  • Stage IVC Laryngeal Cancer AJCC v8
  • Stage IVC Lip and Oral Cavity Cancer AJCC v8
  • Stage IVC Oropharyngeal (p16-Negative) Carcinoma AJCC v8

NCT number NCT05063552
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Not yet recruiting
Phase Phase 2/Phase 3
Start date January 12, 2022
Completion date December 15, 2027

See also
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