Multicenter Randomized Phase II Study of Erlotinib, Cisplatin and Radiotherapy Versus Cisplatin and Radiotherapy in Patients With Stage III and IV Squamous Cell Carcinoma of the Head and Neck
18 Years
N/A
Both
Stage III Squamous Cell Carcinoma of the Hypopharynx, Stage III Squamous Cell Carcinoma of the Larynx, Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage III Squamous Cell Carcinoma of the Nasopharynx, Stage III Squamous Cell Carcinoma of the Oropharynx, Stage IV Squamous Cell Carcinoma of the Hypopharynx, Stage IV Squamous Cell Carcinoma of the Larynx, Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity, Stage IV Squamous Cell Carcinoma of the Nasopharynx, Stage IV Squamous Cell Carcinoma of the Oropharynx
Trial Information
Multicenter Randomized Phase II Study of Erlotinib, Cisplatin and Radiotherapy Versus Cisplatin and Radiotherapy in Patients With Stage III and IV Squamous Cell Carcinoma of the Head and Neck
PRIMARY OBJECTIVES:
I. Compare the complete response rate in patients with locally advanced head and neck
cancer, treated with cisplatin, radiotherapy and erlotinib (erlotinib hydrochloride) versus
cisplatin and radiotherapy alone.
SECONDARY OBJECTIVES:
I. Evaluate whether the addition of erlotinib increases the acute and long term toxicities
of cisplatin and radiotherapy, in patients with locally advanced head and neck cancer.
II. Compare the disease-free and overall survivals of patients with locally advanced head
and neck cancer treated with cisplatin and radiotherapy, with and without erlotinib.
III. Evaluate whether the symptomatic improvement observed in the first week of erlotinib
alone predicts for complete response and long term disease control.
IV. Correlate epidermal growth factor receptor (EGFR), p16 and excision repair
cross-complementing 1 (ERCC-1) expression with response outcome to therapy with cisplatin
and radiation with and without erlotinib.
V. Identify other molecular correlates that may be relevant in the pathogenesis of squamous
cell carcinoma of head and neck (SCCHN) or response to therapy.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive cisplatin intravenously (IV) on days 1, 22, and 43 and undergo
3-dimensional conformal or intensity modulated radiotherapy once daily, 5 days per week, on
days 1-47. Patients also receive erlotinib hydrochloride orally (PO) once daily (QD) on days
-7 to 47.
ARM II: Patients receive cisplatin and undergo radiotherapy as in Arm I.
Within 10-14 weeks after completion of study treatment, patients with N2 or N3 disease at
the time of screening undergo a neck dissection.
After completion of study treatment, patients are followed up periodically for 5 years.
Inclusion Criteria:
- Cytological or pathological documented squamous cell carcinoma of oral cavity,
oropharynx, larynx, and hypopharynx; patients with nasopharyngeal carcinoma can be
included if the patients have grades I or II tumors according to the World Health
Organization (WHO) classification
- Stage III or IV according to the American Joint Committee on Cancer (AJCC) Cancer
Staging Manual, Sixth Edition (2002)
- Unresectable or resection with significant morbidity
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Measurable Disease, defined according to Response Evaluation Criteria in Solid Tumors
(RECIST) Criteria
- Bilirubin =< 1.5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN
- Calculated creatinine clearance >= 55ml/min (using the Cockcroft-Gault formula)
- Platelet count >= 100 x 10^9 /L
- Absolute neutrophil count (ANC) >= 1.25 x 10^9 /L
- Signed informed consent
- Male and female patients with reproductive potential must use an acceptable
contraceptive method
- Authorization from a dentist to begin radiation therapy
Exclusion Criteria:
- Second primary malignancy that is clinically detectable or clinically significant at
the time of consideration for study enrollment
- Inability or unwillingness to comply with radiotherapy
- Evidence of clinically significant congestive heart failure; patients must be able to
tolerate hydration required during cisplatin chemotherapy
- Diarrhea > grade 1 at the time of enrollment
- Prior radiotherapy, chemotherapy, or investigational treatment for squamous cell
carcinoma of head and neck
- Prior treatment with an investigational or marketed inhibitor of the EGFR pathway
- Use of cytochrome P450 3A4 (CYP3A4) inducers
- Presence of systemic metastases (M1)
- Pregnant or breast-feeding women
- Known human immunodeficiency virus (HIV) infection
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Comparison of the Percentage of Participants With a Complete Response in Each Treatment Arm
Outcome Description:
Complete response requires both a pathological complete response (independent of observer) and a complete response radiologically (RECIST 1.0).
Outcome Time Frame:
12 weeks after the completion of therapy
Safety Issue:
No
Principal Investigator
Renato Martins
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Authority:
United States: Institutional Review Board
Study ID:
6106
NCT ID:
NCT00410826
Start Date:
June 2006
Completion Date:
Related Keywords:
- Stage III Squamous Cell Carcinoma of the Hypopharynx
- Stage III Squamous Cell Carcinoma of the Larynx
- Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity
- Stage III Squamous Cell Carcinoma of the Nasopharynx
- Stage III Squamous Cell Carcinoma of the Oropharynx
- Stage IV Squamous Cell Carcinoma of the Hypopharynx
- Stage IV Squamous Cell Carcinoma of the Larynx
- Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
- Stage IV Squamous Cell Carcinoma of the Nasopharynx
- Stage IV Squamous Cell Carcinoma of the Oropharynx
- Carcinoma
- Carcinoma, Squamous Cell
- Head and Neck Neoplasms
- Laryngeal Diseases
- Hypopharyngeal Neoplasms
- Laryngeal Neoplasms
- Oropharyngeal Neoplasms
- Nasopharyngeal Neoplasms
Name | Location |
|---|---|
| Medical University of South Carolina | Charleston, South Carolina 29425-0721 |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle, Washington 98109 |
| University of North Carolina | Chapel Hill, North Carolina 27599 |
| Multicare Health System | Tacoma, Washington 98415 |
| University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami, Florida 33136 |
| Alaska Oncology and Hematology LLC | Anchorage, Alaska 99508 |
| University of New Mexico Health Science CCOP | Albuquerque, New Mexico 87131 |
| New Hanover Radiation Oncology Center | Wilmington, North Carolina 28401 |
| University of Tennessee Cancer Institute-Boston Cancer Group PLC | Memphis, Tennessee 38104 |
