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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Comprehensive Cancer Center of Wake Forest University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT00721513
First received: July 23, 2008
Last updated: July 21, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Biological: cetuximab
Drug: cisplatin
Drug: docetaxel
Drug: fluorouracil
Procedure: computed tomography
Procedure: positron emission tomography
Procedure: quality-of-life assessment
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective response rate [ Designated as safety issue: No ]
  • Best overall response rate [ Designated as safety issue: No ]
  • Overall survival and local-regional control [ Designated as safety issue: No ]
  • Incidence of distant metastasis [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]
  • Acute and chronic toxicities [ Designated as safety issue: Yes ]
  • Quality of life and swallowing [ Designated as safety issue: No ]

Estimated Enrollment: 46
Study Start Date: September 2008
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00721513

Locations
United States, North Carolina
Wake Forest University Comprehensive Cancer Center Recruiting
Winston-Salem, North Carolina, United States, 27157-1096
Contact: Clinical Trials Office - Wake Forest University Comprehensive    336-713-6771      
Sponsors and Collaborators
Comprehensive Cancer Center of Wake Forest University
Investigators
Principal Investigator: Mercedes Porosnicu, MD Comprehensive Cancer Center of Wake Forest University
  More Information

Additional Information:
No publications provided

Responsible Party: Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier: NCT00721513     History of Changes
Other Study ID Numbers: CCCWFU 60108, P30CA012197, CCCWFU-60108, CCCWFU-IRB- IRB00005784, SANOFI-AVENTIS-CCCWFU-60108
Study First Received: July 23, 2008
Last Updated: July 21, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Comprehensive Cancer Center of Wake Forest University:
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

Additional relevant MeSH terms:
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Neoplasms by Site
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Docetaxel
Cetuximab
Cisplatin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 16, 2014