This phase II trial studies how well paclitaxel and carboplatin before radiation therapy with paclitaxel works in treating human papillomavirus (HPV)-positive patients with stage III-IV oropharynx, hypopharynx, or larynx cancer. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high energy x rays to kill tumor cells. Giving paclitaxel and carboplatin before radiation therapy with paclitaxel may kill more tumor cells.
PRIMARY OBJECTIVES: I. To determine the progression-free survival at 2 years in patients with HPV-positive head and neck squamous cell carcinoma (HNSCC) who receive induction chemotherapy followed by dose de-intensified chemoradiotherapy. SECONDARY OBJECTIVES: I. To determine the overall survival and local-regional control for patients with HPV-positive HNSCC who receive induction chemotherapy and dose de-intensified chemoradiotherapy. II. To determine the incidence of acute grade 3+ mucosal and esophageal toxicity associated with attenuated concurrent chemoradiotherapy in patients with HPV-positive HNSCC. III. To determine the incidence of late toxicity in patients with HPV-positive HNSCC who receive the dose de-intensified chemoradiotherapy. IV. To estimate the incidence of all toxicity (hematologic and non-hematologic) associated with protocol treatment for all patients on trial. V. To estimate the response rate of HPV-positive to induction chemotherapy using carboplatin and paclitaxel. VI. To determine the effect of reduced radiation dose on short-term and long-term quality of life among patients treated by chemoradiotherapy. OUTLINE: INDUCTION: Patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30 minutes. Treatment repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. CHEMORADIOTHERAPY: At least 2 weeks after completion of induction chemotherapy, patients receive paclitaxel IV over 1 hour weekly and undergo intensity-modulated radiation therapy (IMRT) daily 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 6, 9, and 12 months, every 3 months for 1 year, and then every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Given IV
Given IV
Undergo IMRT
Ancillary studies
Jonsson Comprehensive Cancer Center
Los Angeles, California, United States
Progression-free survival
The true 2-year progression-free survival rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression or death 2 years from registration. A 95% confidence interval (CI) for the true progression-free survival rate will be constructed using the Duffy-Santner approach. However, Kaplan-Meier methodology will be used to estimate the final 2-year progression-free survival rate and its 95% CI in case there are censored patients.
Time frame: From date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause, assessed at 2 years
Overall survival
Time to event distributions will be estimated using the Kaplan-Meier method.
Time frame: The time from registration to death, assessed up to 5 years
Local-regional control
The 2-year rates of local-regional control will be calculated along with 95% CI for HPV-positive patients receiving the dose de-intensified therapy. It will also be compared with the rate from historical controls using a one-sided Z-test.
Time frame: 2 years
Incidence of mucosal and esophageal >= grade 3 toxicity graded according to the National Cancer Institute Common Terminology for Adverse Events version 4.0 (NCI CTCAE v4.0)
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, protocol treatment delivery (PTD) and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Time frame: Up to 12 weeks after chemoradiotherapy
Incidence of other >= grade 3 toxicity graded according to NCI CTCAE v4.0
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, PTD and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Time frame: Up to 12 weeks after chemoradiotherapy
PTD
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, PTD and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Time frame: Up to 5 years
Incidence of death
Rates and 95% CIs of grade 3+ mucosal and esophageal toxicity, late toxicity, other toxicities, PTD and death during or within 30 days of discontinuation of protocol treatment will be calculated for the patients receiving the dose de-intensified therapy.
Time frame: During or within 30 days of discontinuation of protocol treatment
Quality of life as assessed by Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) and University of Washington Quality of Life (UWQol)
Descriptive statistics for quality of life measurements will also be obtained, using mean and standard deviation for continuous measures and frequency tables for categorical measures.
Time frame: Up to 5 years
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