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

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
erlotinib hydrochloride
cisplatin
3-dimensional conformal radiation therapy
intensity-modulated radiation therapy
quality-of-life assessment
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage III Squamous Cell Carcinoma of the Hypopharynx

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Alaska Oncology and Hematology LLC
  • University of Miami Miller School of Medicine-Sylvester Cancer Center
  • University of New Mexico Health Science CCOP
  • University of North Carolina
  • New Hanover Radiation Oncology Center
  • Medical University of South Carolina
  • University of Tennessee Cancer Institute-Boston Cancer Group PLC
  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  • Multicare Health System

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (chemo, radiotherapy, enzyme inhibitor/radiosensitizer)

Arm II (chemotherapy, radiotherapy)

Arm Description

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.

Patients receive cisplatin and radiotherapy as in Arm I.

Outcomes

Primary Outcome Measures

Comparison of the Percentage of Participants With a Complete Response in Each Treatment Arm
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
Progression Free Survival of Patients With Locally Advanced Head and Neck Cancer Treated With Cisplatin and Radiotherapy, With and Without Erlotinib Hydrochloride
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

Full Information

First Posted
December 11, 2006
Last Updated
May 8, 2013
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00410826
Brief Title
Cisplatin and Radiation Therapy With or Without Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Head and Neck Cancer
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
June 2006 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
204 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (chemo, radiotherapy, enzyme inhibitor/radiosensitizer)
Arm Type
Experimental
Arm Description
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 Title
Arm II (chemotherapy, radiotherapy)
Arm Type
Active Comparator
Arm Description
Patients receive cisplatin and radiotherapy as in Arm I.
Intervention Type
Drug
Intervention Name(s)
erlotinib hydrochloride
Other Intervention Name(s)
CP-358,774, erlotinib, OSI-774
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
cisplatin
Other Intervention Name(s)
CACP, CDDP, CPDD, DDP
Intervention Description
Given IV
Intervention Type
Radiation
Intervention Name(s)
3-dimensional conformal radiation therapy
Other Intervention Name(s)
3D-CRT, conformal radiation therapy
Intervention Description
35 fractions
Intervention Type
Radiation
Intervention Name(s)
intensity-modulated radiation therapy
Other Intervention Name(s)
IMRT
Intervention Description
35 fractions
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
Other Intervention Name(s)
quality of life assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Comparison of the Percentage of Participants With a Complete Response in Each Treatment Arm
Description
Complete response requires both a pathological complete response (independent of observer) and a complete response radiologically (RECIST 1.0).
Time Frame
12 weeks after the completion of therapy
Secondary Outcome Measure Information:
Title
Safety as Assessed Through Summaries of Adverse Events and Laboratory Test Results by Treatment Arm
Time Frame
30 days after the completion of therapy
Title
Progression Free Survival of Patients With Locally Advanced Head and Neck Cancer Treated With Cisplatin and Radiotherapy, With and Without Erlotinib Hydrochloride
Description
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
Time Frame
Every 3 months for up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Renato Martins
Organizational Affiliation
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Alaska Oncology and Hematology LLC
City
Anchorage
State/Province
Alaska
ZIP/Postal Code
99508
Country
United States
Facility Name
University of Miami Miller School of Medicine-Sylvester Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of New Mexico Health Science CCOP
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
New Hanover Radiation Oncology Center
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
University of Tennessee Cancer Institute-Boston Cancer Group PLC
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38104
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Multicare Health System
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98415
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
25057165
Citation
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.
Results Reference
derived
PubMed Identifier
24064970
Citation
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.
Results Reference
derived
PubMed Identifier
23460709
Citation
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.
Results Reference
derived

Learn more about this trial

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

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