Clinical trial NCT01084083
Conditions: Head and Neck Cancer Precancerous Condition
Keywords: human papilloma virus infection stage III squamous cell carcinoma of the oropharynx stage IV squamous cell carcinoma of the oropharynx tongue cancer
Sponsor: Eastern Cooperative Oncology Group
Start date: 2010-08-11; Completion date: 2015-01-01
Enrollment: 90 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high energy x-rays to kill tumor cells. Giving paclitaxel, cisplatin, and cetuximab together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying paclitaxel, cisplatin, and cetuximab to see how well they work when followed by cetuximab and two different doses of intensity-modulated radiation therapy in treating patients with HPV-associated stage III or stage IV cancer of the oropharynx that can be removed by surgery.

Detailed description:
OBJECTIVES:

Primary

* To evaluate the efficacy of induction therapy comprising paclitaxel, cisplatin, and cetuximab followed by cetuximab in combination with low-dose or standard-dose intensity-modulated radiotherapy, as measured by 2-year progression-free survival (PFS), in patients with human papillomavirus(HPV)-associated resectable stage III-IVB squamous cell carcinoma of the oropharynx.

Secondary

* To assess overall survival.
* To evaluate the objective response, local control, and metastatic rate.
* To evaluate early and late toxicities of treatment.

Tertiary

* To evaluate quality of life and speech and swallowing function as measured by Functional Assessment of Cancer Therapy - General (FACT-G), Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN), and Vanderbilt Head and Neck Symptom Survey (VHNSS).
* To assess the effect of treatment-induced fatigue on general physical functioning in patients with head and neck cancer.
* To correlate functional decline with clinical, physical, and biologic correlatives.
* To evaluate radiation-resistance markers, including ERCC1 single nucleotide polymorphism and protein expression, and to correlate them with treatment efficacy.
* To demonstrate the usefulness of biomarkers, including ERCC1, epidermal growth factor receptor (EGFR), cytokine and chemokine markers, and plasma transforming growth factor alpha (TGFA) and transforming growth factor beta (TGFB) levels, in predicting progression-free survival (PFS) and other outcome parameters.
* To evaluate the correlation between the efficacy of cetuximab and polymorphisms in FcγR-receptors.
* To evaluate functional outcome and biological parameters, including telomere length, angiotensin-converting enzyme polymorphism, and C-reactive protein level.

OUTLINE: This is a multicenter study.

* Induction therapy: Patients receive cisplatin intravenously (IV) over 1 hour on day 1 and paclitaxel IV over 3 hours and cetuximab IV over 1-2 hours on days 1, 8, and 15. Treatment repeats every 21 days for 3 courses. Patients then undergo evaluation of response to induction therapy. Patients with a clinical complete response (CR) at the primary tumor site proceed to group 1 of concurrent radiotherapy and cetuximab. Patients with a clinical partial response (PR) or stable disease (SD) at the primary tumor site or those with grossly positive disease at the primary tumor site proceed to group 2 of concurrent radiotherapy and cetuximab.
* Concurrent radiotherapy and cetuximab: Treatment begins 14-21 days after the last day of induction therapy.

  * Group 1 (CR): Patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks.
  * Group 2 (PR, SD, or grossly positive disease): Patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks.

Patients complete questionnaires assessing fatigue, physical function, weight loss, quality of life, head and neck symptom burden, and speech and swallowing function at baseline and at 1, 6, 12, and 24 months after completion of study treatment.

Tumor tissue and serum samples may be collected periodically for correlative laboratory studies.

After completion of study treatment, patients are followed up periodically for 3 years.

PROJECTED ACCRUAL: 83 patients

Arms: arm 1: After induction therapy with Paclitaxel and Cisplatin, patients undergo low-dose intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 5 weeks (27 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 6 weeks. arm 2: After induction therapy with Paclitaxel and Cisplatin, patients undergo standard-dose IMRT 5 days per week for approximately 6 weeks (33 fractions). Patients also receive cetuximab IV over 1-2 hours once weekly for 7 weeks.
Interventions: intervention 1: cetuximab intervention 2: intensity-modulated radiation therapy (IMRT) intervention 3: Paclitaxel intervention 4: Cisplatin
Intervention descriptions: intervention 1: Given IV intervention 2: Patients undergo low-dose OR standard dose IMRT based on their clinical response to induction therapy intervention 3: Given IV, 90 mg/m\^2 on days 1, 8 and 15 intervention 4: Given IV, 75 mg/m\^2 on day 1

Protocol documents: