Cisplatin and Radiation Therapy With or Without Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Head and Neck Cancer

Phase 2

Completed

• Conditions: Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III 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 Squamous Cell Carcinoma of the Lip and Oral Cavity; 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
• Interventions: Drug: erlotinib hydrochloride; Drug: cisplatin; Radiation: 3-dimensional conformal radiation therapy; Radiation: intensity-modulated radiation therapy; Procedure: quality-of-life assessment

• Registration Number: NCT00410826
• Lead Sponsor: University of Washington

Brief Summary

This randomized phase II trial is studying cisplatin and radiation therapy together with or without erlotinib hydrochloride to compare how well they work in treating patients with stage III or stage IV head and neck cancer. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It may also make tumor cells more sensitive to radiation therapy. Giving cisplatin and radiation therapy together with erlotinib hydrochloride may kill more tumor cells. It is not yet known whether cisplatin and radiation therapy are more effective with or without erlotinib hydrochloride in treating head and neck cancer

Detailed Description

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.

Study Timeline

• Study Start: 2006-06
• Study First Submitted: 2006-12-11
• Study First Submitted QC: 2006-12-11
• Study First Posted: 2006-12-13
• Primary Completion: 2012-05
• Results First Submitted: 2012-12-14
• Results First Submitted QC: 2013-02-20
• Results First Posted: 2013-04-02
• Status Verified: 2013-05
• Last Update Submitted: 2013-05-08
• Last Update Posted: 2013-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 204

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (chemo, radiotherapy, enzyme inhibitor/radiosensitizer)	intensity-modulated radiation therapy	Patients receive cisplatin 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 PO once daily on days -7 to 47.
Arm I (chemo, radiotherapy, enzyme inhibitor/radiosensitizer)	erlotinib hydrochloride	Patients receive cisplatin 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 PO once daily on days -7 to 47.
Arm I (chemo, radiotherapy, enzyme inhibitor/radiosensitizer)	cisplatin	Patients receive cisplatin 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 PO once daily on days -7 to 47.
Arm I (chemo, radiotherapy, enzyme inhibitor/radiosensitizer)	3-dimensional conformal radiation therapy	Patients receive cisplatin 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 PO once daily on days -7 to 47.
Arm I (chemo, radiotherapy, enzyme inhibitor/radiosensitizer)	quality-of-life assessment	Patients receive cisplatin 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 PO once daily on days -7 to 47.
Arm II (chemotherapy, radiotherapy)	cisplatin	Patients receive cisplatin and radiotherapy as in Arm I.
Arm II (chemotherapy, radiotherapy)	3-dimensional conformal radiation therapy	Patients receive cisplatin and radiotherapy as in Arm I.
Arm II (chemotherapy, radiotherapy)	intensity-modulated radiation therapy	Patients receive cisplatin and radiotherapy as in Arm I.
Arm II (chemotherapy, radiotherapy)	quality-of-life assessment	Patients receive cisplatin and radiotherapy as in Arm I.

Primary Outcome Measures

Name	Time	Method
Comparison of the Percentage of Participants With a Complete Response in Each Treatment Arm	12 weeks after the completion of therapy	Complete response requires both a pathological complete response (independent of observer) and a complete response radiologically (RECIST 1.0).

Secondary Outcome Measures

Name	Time	Method
Safety as Assessed Through Summaries of Adverse Events and Laboratory Test Results by Treatment Arm	30 days after the completion of therapy
Progression Free Survival of Patients With Locally Advanced Head and Neck Cancer Treated With Cisplatin and Radiotherapy, With and Without Erlotinib Hydrochloride	Every 3 months for up to 5 years	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Trial Locations

Locations (9)

New Hanover Radiation Oncology Center; 🇺🇸 Wilmington, North Carolina, United States

University of North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States

Alaska Oncology and Hematology LLC; 🇺🇸 Anchorage, Alaska, United States

University of New Mexico Health Science CCOP; 🇺🇸 Albuquerque, New Mexico, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center; 🇺🇸 Miami, Florida, United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

University of Tennessee Cancer Institute-Boston Cancer Group PLC; 🇺🇸 Memphis, Tennessee, United States

Multicare Health System; 🇺🇸 Tacoma, Washington, United States