Randomized Phase II/III Trial of Adjuvant Radiation Therapy With Cisplatin, Docetaxel-Cetuximab, or Cisplatin-Atezolizumab in Pathologic High-Risk Squamous Cell Cancer of the Head and Neck
Overview
- Phase
- Phase 2
- Intervention
- Biopsy Procedure
- Conditions
- Oropharyngeal p16INK4a-Negative Squamous Cell Carcinoma
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 613
- Locations
- 647
- Primary Endpoint
- Disease-free survival (Phase II)
- Status
- Recruiting
- Last Updated
- 15 days ago
Overview
Brief Summary
This phase II/III trial studies how well radiation therapy works when given together with cisplatin, docetaxel, cetuximab, and/or atezolizumab after surgery in treating patients with high-risk stage III-IV head and neck cancer the begins in the thin, flat cells (squamous cell). Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as cisplatin and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cetuximab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. 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. The purpose of this study is to compare the usual treatment (radiation therapy with cisplatin chemotherapy) to using radiation therapy with docetaxel and cetuximab chemotherapy, and using the usual treatment plus an immunotherapy drug, atezolizumab.
Detailed Description
PRIMARY OBJECTIVES: I. To select the better docetaxel-based experimental arm to improve disease-free survival (DFS) over the control arm of radiation and cisplatin. (Phase II) (COMPLETE AS OF 20-MAR-2020) II. To determine if the combination of docetaxel-cetuximab and intensity-modulated radiation therapy (IMRT) is superior in terms of overall survival (OS) compared to standard cisplatin and IMRT in the adjuvant treatment of pathologic high risk, human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). (Phase III) III. To determine if the combination of atezolizumab, cisplatin, and IMRT is superior in terms of OS compared to standard cisplatin and IMRT in the adjuvant treatment of pathologic high risk, HPV-negative HNSCC. (Phase III) SECONDARY OBJECTIVES: I. To compare disease-free survival (DFS) between each experimental arm and the control arm. (Phase III) II. To determine whether each experimental arm improves local-regional disease control and the rate of distant metastasis. (Phase III) III. To compare acute toxicity profiles between each experimental arm and the control arm. (Phase III) IV. To compare late toxicity profiles at 1, 3, and 5 years after treatment. (Phase III) V. To assess long term DFS and OS between each experimental arm and the control arm. (Phase III) VI. To compare symptom burden, as measured by the MD Anderson Symptom Inventory - Head and Neck (MDASI-HN) (primary patient reported outcome \[PRO\]), and quality of life, as measured by the Functional Assessment of Cancer Therapy - Head and Neck (FACT-H\&N) (secondary PRO), between each experimental arm and the control arm. (Phase III) EXPLORATORY OBJECTIVE: I. To collect blood and tissue specimens for future translational research. (Phase III) OUTLINE: Patients are randomized to 1 of 3 arms - Phase II (Arms 1, 2 or 3) and for Phase III (Arms 1, 3 or 4). ARM 1: Patients undergo intensity modulated radiation therapy (IMRT) once daily (QD) five days a week for 6 weeks and receive concurrent cisplatin intravenously (IV) over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. ARM 2: Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. (CLOSED AS OF 20-MAR-2020) ARM 3: Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and concurrently receive docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. ARM 4: Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. All patients undergo collection of blood samples during screening and throughout the study and may undergo computed tomography (CT) scans and/or magnetic resonance imaging (MRI) and biopsy as clinically indicated on study. After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •PHASE II INCLUSION CRITERIA (COMPLETE AS OF 20-MAR-2020)
- •Pathologically (histologically or cytologically) proven diagnosis of head and neck squamous cell carcinoma (HNSCC) involving the oral cavity (excluding lips), oropharynx (p16 negative), larynx, or hypopharynx
- •Patients must have undergone gross total surgical resection of high-risk oral cavity, oropharynx (p16 negative), larynx, or hypopharynx within 63 days prior to registration; Note: patients may have biopsy under general anesthesia in an operating room followed by definitive ablative cancer surgery representing gross total resection; the gross total resection has to be done within 63 days prior to registration; if, however, patients have ablative resection but shortly recur or are determined to have persisting disease requiring re-resection to achieve gross total resection, then the patient is not eligible
- •Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer at the primary tumor resection margin (tumor on ink)
- •Pathologic stage III or IV HNSCC, including no distant metastases, based upon the following minimum diagnostic workup:
- •General history and physical examination by a radiation oncologist and/or medical oncologist within 84 days prior to registration;
- •Examination by an ear nose throat (ENT) or head \& neck surgeon prior to surgery; a laryngopharyngoscopy (mirror and/or fiber optic and/or direct procedure), if appropriate, is recommended but not required; intra-operative examination is acceptable documentation
- •Pre-operative (op) Imaging of the head and neck: A neck computed tomography (CT) (with contrast) or CT/positron emission tomography (PET) (with contrast) and/or an magnetic resonance imaging (MRI) of the neck (T1 with gadolinium and T2) within 84 days prior to surgery; Note: this imaging data (diagnostic pre-operative scan showing gross disease) is to be submitted in Digital Imaging and Communications in Medicine (DICOM) format via TRIAD; the report is to be uploaded into Rave
- •Chest CT scan (with or without contrast) or CT/PET that includes the chest (with or without contrast) either within 84 days prior to surgery or within 120 days prior to registration; Note: if the CT/PET with or without contrast is done within 84 days prior to surgery, it fulfills the chest imaging requirement
- •Zubrod performance status of 0-1 within 14 days prior to registration
Exclusion Criteria
- •PHASE II EXCLUSION CRITERIA (COMPLETE AS OF 20-MAR-2020)
- •Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 1095 days (3 years); noninvasive cancers (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible) are permitted even if diagnosed and treated \< 3 years ago
- •Patients with simultaneous primaries or bilateral tumors are excluded, with the exception of patients with bilateral tonsil cancers or patients with T1-2, N0, M0 resected differentiated thyroid carcinoma, who are eligible
- •Prior systemic chemotherapy or anti-epidermal growth factor (EGF) therapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
- •Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
- •Severe, active co-morbidity, defined as follows:
- •Unstable angina and/or congestive heart failure requiring hospitalization within 6 months prior to registration
- •Transmural myocardial infarction within 6 months prior to registration
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
- •Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
Arms & Interventions
Arm 1 (IMRT, cisplatin)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Biopsy Procedure
Arm 4 (IMRT, cisplatin, atezolizumab)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Survey Administration
Arm 1 (IMRT, cisplatin)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Computed Tomography
Arm 1 (IMRT, cisplatin)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Biospecimen Collection
Arm 2 (IMRT, docetaxel)
Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Intervention: Docetaxel
Arm 2 (IMRT, docetaxel)
Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Intervention: Biospecimen Collection
Arm 2 (IMRT, docetaxel)
Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Intervention: Survey Administration
Arm 1 (IMRT, cisplatin)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Survey Administration
Arm 3 (IMRT, docetaxel, cetuximab)
Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Intensity-Modulated Radiation Therapy
Arm 1 (IMRT, cisplatin)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Intensity-Modulated Radiation Therapy
Arm 1 (IMRT, cisplatin)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Cisplatin
Arm 1 (IMRT, cisplatin)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Magnetic Resonance Imaging
Arm 2 (IMRT, docetaxel)
Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Intervention: Computed Tomography
Arm 3 (IMRT, docetaxel, cetuximab)
Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Survey Administration
Arm 4 (IMRT, cisplatin, atezolizumab)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Biopsy Procedure
Arm 4 (IMRT, cisplatin, atezolizumab)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Biospecimen Collection
Arm 3 (IMRT, docetaxel, cetuximab)
Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Biospecimen Collection
Arm 3 (IMRT, docetaxel, cetuximab)
Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Computed Tomography
Arm 3 (IMRT, docetaxel, cetuximab)
Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Magnetic Resonance Imaging
Arm 4 (IMRT, cisplatin, atezolizumab)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Computed Tomography
Arm 4 (IMRT, cisplatin, atezolizumab)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Intensity-Modulated Radiation Therapy
Arm 2 (IMRT, docetaxel)
Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Intervention: Intensity-Modulated Radiation Therapy
Arm 2 (IMRT, docetaxel)
Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and/or MRI, and collection of blood during follow-up. (CLOSED AS OF 20-MAR-2020)
Intervention: Magnetic Resonance Imaging
Arm 4 (IMRT, cisplatin, atezolizumab)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Magnetic Resonance Imaging
Arm 3 (IMRT, docetaxel, cetuximab)
Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Biopsy Procedure
Arm 4 (IMRT, cisplatin, atezolizumab)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Atezolizumab
Arm 4 (IMRT, cisplatin, atezolizumab)
Patients undergo IMRT QD five days a week for 6 weeks and receive concurrent cisplatin IV over 1-2 hours once weekly for 6 weeks. Starting 1 week before IMRT, patients also receive atezolizumab IV over 30-60 minutes every 3 weeks for up to 8 doses (weeks -1, 3, 6, 9, 12, 15, 18, and 21) in the absence of disease progression and unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Cisplatin
Arm 3 (IMRT, docetaxel, cetuximab)
Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Docetaxel
Arm 3 (IMRT, docetaxel, cetuximab)
Patients receive cetuximab IV over 120 minutes on week 1 and over 60 minutes once weekly on weeks 2-7. Patients undergo IMRT as in Arm I and receive concurrent docetaxel once weekly for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples during screening and throughout the study and may undergo CT scans and/or MRI and biopsy as clinically indicated on study.
Intervention: Cetuximab
Outcomes
Primary Outcomes
Disease-free survival (Phase II)
Time Frame: From date of randomization until date of local-regional recurrence, distant metastasis or death due to any cause, assessed up to 7 years
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a one-sided log rank test.
Overall survival (Phase III)
Time Frame: From date of randomization to death due to any cause, assessed up to 7 years
Estimated using the Kaplan-Meier method for each arm. Their distributions will be compared between treatment arms with a one-sided log rank test. Multivariate analysis will be performed using the Cox proportional hazards model.
Secondary Outcomes
- Local-regional failure(From date of randomization until date of local-regional recurrence, assessed up to 7 years)
- Distant metastasis(From date of randomization to date of distant metastasis, assessed up to 7 years)
- Toxicity(From start of treatment to death or last follow-up)
- Patient-reported outcome, symptom burden(Time from randomization to a first recovery within at least one MID unit of total symptom severity compared to the baseline (reference) score)
- Quality of life(Baseline and 1 year post radiation therapy)