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Docetaxel, Cisplatin, and Fluorouracil Followed By Cetuximab and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

Phase 2
Completed
Conditions
Head and Neck Cancer
Interventions
Biological: cetuximab
Procedure: computed tomography
Procedure: positron emission tomography
Procedure: quality-of-life assessment
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
Registration Number
NCT00721513
Lead Sponsor
Wake Forest University Health Sciences
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, 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 combination chemotherapy together with cetuximab and radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving docetaxel, cisplatin, and fluorouracil together with cetuximab and radiation therapy works in treating patients with locally advanced head and neck cancer.

Detailed Description

OBJECTIVES:

Primary

* Evaluate the progression-free survival of patients with locally advanced squamous cell carcinoma of the head and neck treated with induction chemotherapy comprising docetaxel, cisplatin, and fluorouracil followed by concurrent cetuximab and radiotherapy.

Secondary

* Assess the objective response rate in patients treated with this regimen.

* Assess the best overall response rate, overall survival, local-regional control, and distant failure in patients treated with this regimen.

* Assess the acute and long-term toxicity associated with this regimen in these patients.

* Assess quality of life and swallowing in patients treated with this regimen.

* Determine the accuracy of PET/CT scan in evaluating objective response; in detecting residual disease at primary sites and nodes; in guiding the recommendation for salvage surgery or for neck dissection; and in early detection of recurrent or metastatic disease.

OUTLINE: Patients are stratified according to nodal status (N2b-c or N3 vs N0-2a), tumor characteristics of invasiveness (present vs absent), human papilloma virus (HPV) status (positive vs negative), and primary tumor site (hypopharynx vs larynx vs oropharynx).

Patients receive induction chemotherapy comprising docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1 and fluorouracil IV continuously on days 1-4. Treatment repeats every 3 weeks for up to 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-4 weeks after completion of induction chemotherapy, patients receive cetuximab IV once weekly for 7 weeks. Beginning 1 week after the first dose of cetuximab, patients undergo concurrent intensity-modulated radiotherapy or conventional 3-dimensional radiotherapy once or twice daily 5-6 days a week for up to 6 weeks. Patients with persistent disease undergo salvage resection of the primary tumor and/or neck dissection approximately 3 months after the completion of radiotherapy.

Patients undergo quality of life and swallowing evaluations periodically.

Patients undergo PET/CT scan at baseline, before beginning radiotherapy, at 6-8 weeks after completion of study treatment, every 6 months for 5 years, and then annually thereafter.

After completion of study treatment, patients are followed at 4 and 8 weeks, every 2 months for 2 years, every 3 months for 1 year, and then every 6 months thereafter.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TPFChemotherapy + Concomitant Cetuximab & RTcetuximabTaxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab \& Radiation Therapy
TPFChemotherapy + Concomitant Cetuximab & RTintensity-modulated radiation therapyTaxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab \& Radiation Therapy
TPFChemotherapy + Concomitant Cetuximab & RTcomputed tomographyTaxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab \& Radiation Therapy
TPFChemotherapy + Concomitant Cetuximab & RTquality-of-life assessmentTaxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab \& Radiation Therapy
TPFChemotherapy + Concomitant Cetuximab & RT3-dimensional conformal radiation therapyTaxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab \& Radiation Therapy
TPFChemotherapy + Concomitant Cetuximab & RTpositron emission tomographyTaxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab \& Radiation Therapy
TPFChemotherapy + Concomitant Cetuximab & RTcisplatinTaxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab \& Radiation Therapy
TPFChemotherapy + Concomitant Cetuximab & RTdocetaxelTaxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab \& Radiation Therapy
TPFChemotherapy + Concomitant Cetuximab & RTfluorouracilTaxotere/Cisplatinum/5-Fluorouracil (TPF) Chemotherapy Followed by Concomitant Cetuximab \& Radiation Therapy
Primary Outcome Measures
NameTimeMethod
Progression-free Survivalup to 2 years
Secondary Outcome Measures
NameTimeMethod
Number of Participants With Distant Metastasisup to 2 years
Objective Response Rateup to 2 years

Will be measured by CT scan /MRI of the head and neck with corroborative results of direct biopsy of any residual tumor at primary site.

Best Overall Response Rateup to 2 years

Defined as rate of complete and partial responses (at least 30% decrease in the sum of the longest diameter of target lesions), measured by CT scan or MRI of the head and neck after completion of multimodality treatment with induction TPF (Docetaxel, cisplatin and fluorouracil) chemotherapy followed by combined ERT. We will use RECIST (Response Evaluation Criteria In Solid Tumors) (Therasse et al, 2000) for evaluation of response.

MD Anderson Dysphagia InventoryBaseline, pre-radiation therapy and post-radiation therapy, up to 2 years

The MD Anderson Dysphasia Inventory (MDADI) is a survey specifically designed to assess dysphasia. It contains 20 questions directly addressing the swallowing function and several other general questions. The questionnaire asks for participants views about their swallowing ability at baseline, pre-radiation therapy and post-radiation therapy. All questions except for E7 and F2: Strongly Agree = 1 point, Agree = 2 points, No Opinion = 3 points, Disagree = 4 points, Strongly Disagree. E7 and F2: Strongly agree = 5 points, Agree = 4 points, no opinion = 3 points, disagree = 2 points, strongly disagree = 1 point. Scores range from 20 (extremely low-functioning) to 100 (high-functioning).

Overall Survivalup to 2 years
Quality of Life - Functional Assessment of Cancer Therapy - General (FACT-G)Baseline, pre-radiation therapy and post-radiation therapy, up to 2 years

Four subscales: physical well-being (PWB; 7-items, score range 0-28), social/family well-being (SWB; 7-items, score range 0-28), emotional well-being (EWB; 6-items, score range 0-24), and functional well-being (FWB; 7-items, score range 0-28). Items are rated on a five-point scale: 0-"not at all", 1- "a little bit", 2-"somewhat", 3- "quite a bit" and 4-"very much". Overall quality of life is the sum of the core items of the FACT-G possible range of 0-108 points. The higher the score the better the quality life. This interval includes 0, we will conclude that there is not conclusive statistical evidence that there is an improvement or worsening. If the interval does not include 0 we can determine whether there was a significant improvement (or worsening) depending on which side of the 0 the interval is on. The total outcome index score (possible range 0-108 points) is the sum of the physical and functional well being and additional concerns categories from the FACT-G.

Number of Participants With Local-Regional Controlup to 2 years
Performance Status Scale for Head and Neck CancerBaseline, pre-radiation therapy and post-radiation therapy, up to 2 years

Consists of assessment of three functions (subscales): Normalcy of diet, eating in public, and understandability of speech. The interviewer rates the patient on each scale based on the patient's responses to targeted questions. Scores range from 0-100 (Full performance (100 score), moderate or severe impairment (≤ 50 score)). The higher the score, the better the ability of the patient to function.

Trial Locations

Locations (1)

Wake Forest University Comprehensive Cancer Center

🇺🇸

Winston-Salem, North Carolina, United States

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