Clinical trial NCT00721513: Docetaxel, Cisplatin, and Fluorouracil Followed By Cetuximab and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer
Official title: Phase II Study to Evaluate the Efficacy and Toxicity of Multimodality Treatment With Induction Taxotere/Cisplatin?5-FU (TPF) Chemotherapy Followed by Concomitant Cetuximab and Radiation Therapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage III verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-07-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion:

* Histologically confirmed (from primary lesion and/or lymph nodes) squamous cell carcinoma (SCC) of the head and neck, including the following subtypes:

  * Oropharynx
  * Hypopharynx
  * Larynx
* Primary site of tumor must not include any of the following:

  * Nasopharynx
  * Sinuses
  * Salivary glands
* Stage III or IV disease that is unresectable (oropharynx, larynx, or hypopharynx) OR that is resectable with organ-sparing goal (oropharynx or hypopharynx)
* Measurable disease by CT scan or MRI
* No definitive evidence of distant metastasis
* ECOG performance status 0-1
* ANC ≥ 1,500/μL
* Platelet count ≥ 100,000/μL
* Hemoglobin ≥ 8 g/dL
* Total bilirubin ≤ normal

  * Except in the case where the elevated total bilirubin is not a sign of liver disease (i.e., Gilbert syndrome), in which case a total bilirubin ≤ 2 times upper limit of normal (ULN) is allowed provided direct bilirubin is ≤ ULN
* AST, ALT, and alkaline phosphate (AP) meeting the following criteria:

  * AP normal AND AST or ALT ≤ 5 times upper limit of normal (ULN)
  * AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
  * AP ≤ 5 times ULN AND AST or ALT normal
* Creatinine ≤ 1.5 mg/dL
* Negative pregnancy test (for women of childbearing potential)
* Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
* Willing to undergo laryngoscopy with biopsy of residual tumor at primary site (as part of a comprehensive evaluation of tumor response after completion of the induction chemotherapy portion of study treatment)

Exclusion:

* History of severe hypersensitivity reaction to docetaxel or to other drugs formulated with polysorbate 80
* Other invasive malignancy within the past 3 years, except nonmelanoma skin cancer
* Prior allergic reaction to the study drug(s)
* Concurrent uncontrolled illness including, but not limited to, any of the following:

  * Ongoing or active infection
  * Psychiatric illness/social situation that would limit compliance with study requirements
  * Significant history of uncontrolled cardiac disease, including any of the following:

    * Uncontrolled hypertension
    * Unstable angina
    * Myocardial infarction within the past 6 months
    * Uncontrolled congestive heart failure
    * Cardiomyopathy with decreased left ventricular ejection fraction (i.e., LVEF \< 45%)
* Uncontrolled condition that, in the opinion of the investigator, would interfere in the safe and timely completion of study procedures
* History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on screening chest CT scan
* HIV positivity
* Pregnant or nursing
* Prior chemotherapy for the study cancer
* Prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
* Prior chemotherapy, biological therapy, or hormone therapy within the last one year
* Prior initial surgical treatment, except diagnostic biopsy of the primary site or nodal sampling of neck disease
* Prior radical or modified neck dissection
* Prior therapy that specifically and directly targets the EGFR pathway
* Concurrent investigational agents

Primary outcomes:
measure: Progression-free Survival
timeFrame: up to 2 years
Secondary outcomes:
measure: Objective Response Rate
timeFrame: up to 2 years
measure: Best Overall Response Rate
timeFrame: up to 2 years
measure: Overall Survival
timeFrame: up to 2 years
measure: Number of Participants With Distant Metastasis
timeFrame: up to 2 years
measure: Quality of Life - Functional Assessment of Cancer Therapy - General (FACT-G)
timeFrame: Baseline, pre-radiation therapy and post-radiation therapy, up to 2 years
measure: Number of Participants With Local-Regional Control
timeFrame: up to 2 years
measure: Performance Status Scale for Head and Neck Cancer
timeFrame: Baseline, pre-radiation therapy and post-radiation therapy, up to 2 years
measure: MD Anderson Dysphagia Inventory
timeFrame: Baseline, pre-radiation therapy and post-radiation therapy, up to 2 years
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Mercedes Porosnicu, MD
role: PRINCIPAL_INVESTIGATOR
References: