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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Renato Martins, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00410826
First received: December 11, 2006
Last updated: May 8, 2013
Last verified: May 2013
  Purpose

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


Condition Intervention Phase
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
Drug: erlotinib hydrochloride
Drug: cisplatin
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
Procedure: quality-of-life assessment
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Comparison of the Percentage of Participants With a Complete Response in Each Treatment Arm [ Time Frame: 12 weeks after the completion of therapy ] [ Designated as safety issue: No ]
    Complete response requires both a pathological complete response (independent of observer) and a complete response radiologically (RECIST 1.0).


Secondary Outcome Measures:
  • Safety as Assessed Through Summaries of Adverse Events and Laboratory Test Results by Treatment Arm [ Time Frame: 30 days after the completion of therapy ] [ Designated as safety issue: Yes ]
  • Progression Free Survival of Patients With Locally Advanced Head and Neck Cancer Treated With Cisplatin and Radiotherapy, With and Without Erlotinib Hydrochloride [ Time Frame: Every 3 months for up to 5 years ] [ Designated as safety issue: No ]
    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


Enrollment: 204
Study Start Date: June 2006
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (chemo, radiotherapy, enzyme inhibitor/radiosensitizer)
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.
Drug: erlotinib hydrochloride
Given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Radiation: 3-dimensional conformal radiation therapy
35 fractions
Other Names:
  • 3D-CRT
  • conformal radiation therapy
Radiation: intensity-modulated radiation therapy
35 fractions
Other Name: IMRT
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Active Comparator: Arm II (chemotherapy, radiotherapy)
Patients receive cisplatin and radiotherapy as in Arm I.
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Radiation: 3-dimensional conformal radiation therapy
35 fractions
Other Names:
  • 3D-CRT
  • conformal radiation therapy
Radiation: intensity-modulated radiation therapy
35 fractions
Other Name: IMRT
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00410826

Locations
United States, Alaska
Alaska Oncology and Hematology LLC
Anchorage, Alaska, United States, 99508
United States, Florida
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
United States, New Mexico
University of New Mexico Health Science CCOP
Albuquerque, New Mexico, United States, 87131
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
New Hanover Radiation Oncology Center
Wilmington, North Carolina, United States, 28401
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Tennessee
University of Tennessee Cancer Institute-Boston Cancer Group PLC
Memphis, Tennessee, United States, 38104
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Multicare Health System
Tacoma, Washington, United States, 98415
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Renato Martins Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided by University of Washington

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Renato Martins, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00410826     History of Changes
Obsolete Identifiers: NCT01009489
Other Study ID Numbers: 6106, NCI-2009-01546
Study First Received: December 11, 2006
Results First Received: December 14, 2012
Last Updated: May 8, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Carcinoma
Laryngeal Neoplasms
Oropharyngeal Neoplasms
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Laryngeal Diseases
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Otorhinolaryngologic Diseases
Pharyngeal Neoplasms
Pharyngeal Diseases
Stomatognathic Diseases
Nasopharyngeal Diseases
Cisplatin
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014