Phase II Trial Of Induction Chemotherapy Followed By Attenuated Chemoradiotherapy For Locally Advanced Head And Neck Squamous Cell Carcinoma Associated With Human Papillomavirus (HPV)
Overview
- Phase
- Phase 2
- Intervention
- paclitaxel
- Conditions
- Human Papilloma Virus Infection
- Sponsor
- Jonsson Comprehensive Cancer Center
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- Progression-free survival
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) diagnosis of HPV-positive squamous cell carcinoma of the oropharynx, hypopharynx, or larynx; HPV-positivity will be defined as tumors that are p16-positive by immunohistochemistry
- •Clinical stage III or IV disease; note: patients with M1 tumors are not eligible
- •Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:
- •History/physical examination within 4 weeks prior to registration, including assessment of weight loss in past 6 months
- •Chest x-ray (or chest computed tomography \[CT\] scan or positron emission tomography \[PET\]/CT scan) within 6 weeks prior to registration
- •CT scan or magnetic resonance imaging (MRI) of the head and neck (of the primary tumor and neck nodes) and PET/CT scan
- •Zubrod performance status 0-1
- •Absolute neutrophil count (ANC) \> 1,800 cells/mm\^3
- •Platelets \> 100,000 cells/mm\^3
- •Hemoglobin (Hgb) \> 8.0 g/dl (note: the use of transfusion or other intervention to achieve Hgb \> 8.0 g/dl is acceptable)
Exclusion Criteria
- •Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
- •Patients with simultaneous primaries or bilateral tumors are excluded
- •Patients who have had initial surgical treatment other than the diagnostic biopsy of the primary site or nodal sampling of the neck disease are excluded
- •Patients with unknown primary tumor sites are excluded
- •Patients who present with a cervical lymph node metastasis of unknown primary origin
- •Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
- •Prior radiotherapy that would result in overlap of radiation therapy fields
- •Primary site of tumor of oral cavity, nasopharynx, nasal cavity, paranasal sinuses, or salivary glands
- •Recurrent head and neck cancer
- •Current uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction
Arms & Interventions
Treatment (paclitaxel, carboplatin, IMRT)
INDUCTION: Patients receive paclitaxel 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 IMRT daily 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: paclitaxel
Treatment (paclitaxel, carboplatin, IMRT)
INDUCTION: Patients receive paclitaxel 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 IMRT daily 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: carboplatin
Treatment (paclitaxel, carboplatin, IMRT)
INDUCTION: Patients receive paclitaxel 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 IMRT daily 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: intensity-modulated radiation therapy
Treatment (paclitaxel, carboplatin, IMRT)
INDUCTION: Patients receive paclitaxel 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 IMRT daily 5 days a week for 5.5 weeks in the absence of disease progression or unacceptable toxicity.
Intervention: quality-of-life assessment
Outcomes
Primary Outcomes
Progression-free survival
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
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.
Secondary Outcomes
- Overall survival(The time from registration to death, assessed up to 5 years)
- Local-regional control(2 years)
- PTD(Up to 5 years)
- Quality of life as assessed by Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N) and University of Washington Quality of Life (UWQol)(Up to 5 years)
- Incidence of death(During or within 30 days of discontinuation of protocol treatment)
- 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)(Up to 12 weeks after chemoradiotherapy)
- Incidence of other >= grade 3 toxicity graded according to NCI CTCAE v4.0(Up to 12 weeks after chemoradiotherapy)