Official Title
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
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
tumour may kill more tumour 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
tumour cells, either by killing the cells or by stopping them from dividing. Cetuximab is a
monoclonal antibody that may interfere with the ability of tumour 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 tumour 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.
Trial Description
Primary Outcome:
- Disease-free survival (DFS) (Phase II)
- Overall survival (OS) (Phase III)
Secondary Outcome:
- Local-regional failure (LRF)
- Distant metastasis (DM)
- Toxicity
- Patient-reported outcome, symptom burden
- Quality of life
PRIMARY OBJECTIVES:
-
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)
- 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)
- 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:
-
To compare disease-free survival (DFS) between each experimental arm and the control arm.
(Phase III)
- To determine whether each experimental arm improves local-regional disease
control and the rate of distant metastasis. (Phase III)
- To compare acute toxicity
profiles between each experimental arm and the control arm. (Phase III)
- To compare late
toxicity profiles at 1, 3, and 5 years after treatment. (Phase III)
- To assess long term
DFS and OS between each experimental arm and the control arm. (Phase III)
- 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:
-
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.
ARM 2: Patients undergo IMRT as in Arm I and receive concurrent docetaxel IV over 60 minutes
once weekly for 6 weeks. (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.
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.
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.
View this trial on ClinicalTrials.gov
