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

NCT ID: NCT00410826

Last Updated: 2013-05-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-30

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

erlotinib hydrochloride

Intervention Type: DRUG

Given orally

cisplatin

Intervention Type: DRUG

Given IV

3-dimensional conformal radiation therapy

Intervention Type: RADIATION

35 fractions

intensity-modulated radiation therapy

Intervention Type: RADIATION

35 fractions

quality-of-life assessment

Intervention Type: PROCEDURE

Ancillary studies

Arm II (chemotherapy, radiotherapy)

Patients receive cisplatin and radiotherapy as in Arm I.

Group Type: ACTIVE_COMPARATOR

cisplatin

Intervention Type: DRUG

Given IV

3-dimensional conformal radiation therapy

Intervention Type: RADIATION

35 fractions

intensity-modulated radiation therapy

Intervention Type: RADIATION

35 fractions

quality-of-life assessment

Intervention Type: PROCEDURE

Ancillary studies

Interventions

erlotinib hydrochloride

Given orally

Intervention Type: DRUG

cisplatin

Given IV

Intervention Type: DRUG

3-dimensional conformal radiation therapy

35 fractions

Intervention Type: RADIATION

intensity-modulated radiation therapy

35 fractions

Intervention Type: RADIATION

quality-of-life assessment

Ancillary studies

Intervention Type: PROCEDURE

Other Intervention Names

CP-358,774; erlotinib; OSI-774; CACP; CDDP; CPDD; DDP; 3D-CRT; conformal radiation therapy; IMRT; quality of life assessment

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Renato Martins

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Renato Martins

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Alaska Oncology and Hematology LLC

Anchorage, Alaska, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

University of New Mexico Health Science CCOP

Albuquerque, New Mexico, United States

University of North Carolina

Chapel Hill, North Carolina, United States

New Hanover Radiation Oncology Center

Wilmington, North Carolina, 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

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Multicare Health System

Tacoma, Washington, United States

Countries

United States

References

Psyrri A, Rampias T, Vermorken JB. The current and future impact of human papillomavirus on treatment of squamous cell carcinoma of the head and neck. Ann Oncol. 2014 Nov;25(11):2101-2115. doi: 10.1093/annonc/mdu265. Epub 2014 Jul 23.

Reference Type: DERIVED

PMID: 25057165 (View on PubMed)

Bauman JE, Austin MC, Schmidt R, Kurland BF, Vaezi A, Hayes DN, Mendez E, Parvathaneni U, Chai X, Sampath S, Martins RG. ERCC1 is a prognostic biomarker in locally advanced head and neck cancer: results from a randomised, phase II trial. Br J Cancer. 2013 Oct 15;109(8):2096-105. doi: 10.1038/bjc.2013.576. Epub 2013 Sep 24.

Reference Type: DERIVED

PMID: 24064970 (View on PubMed)

Martins RG, Parvathaneni U, Bauman JE, Sharma AK, Raez LE, Papagikos MA, Yunus F, Kurland BF, Eaton KD, Liao JJ, Mendez E, Futran N, Wang DX, Chai X, Wallace SG, Austin M, Schmidt R, Hayes DN. Cisplatin and radiotherapy with or without erlotinib in locally advanced squamous cell carcinoma of the head and neck: a randomized phase II trial. J Clin Oncol. 2013 Apr 10;31(11):1415-21. doi: 10.1200/JCO.2012.46.3299. Epub 2013 Mar 4.

Reference Type: DERIVED

PMID: 23460709 (View on PubMed)

Other Identifiers

NCI-2009-01546

Identifier Type: REGISTRY

Identifier Source: secondary_id

6106

Identifier Type: -

Identifier Source: org_study_id

NCT01009489

Identifier Type: -

Identifier Source: nct_alias