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Bevacizumab and Erlotinib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Primary Purpose

Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bevacizumab
erlotinib hydrochloride
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

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

Inclusion Criteria: Histologically or cytologically confirmed squamous cell cancer of the head and neck Recurrent or metastatic disease Determined to be incurable by surgery or radiotherapy Measurable disease No tumor involvement encasing or too close in proximity to a major artery or vein No known brain metastases No prior or concurrent CNS disease No primary brain tumor Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 12 weeks No history of bleeding diathesis WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 INR less than 1.5 Bilirubin normal AST and ALT no greater than 2.5 times upper limit of normal Creatinine normal Creatinine clearance at least 60 mL/min No significant renal impairment 24-hour urinary protein less than 0.5 g required if more than trace proteinuria at baseline No uncontrolled hypertension No symptomatic congestive heart failure No serious cardiac arrhythmia requiring medication No deep venous thrombosis No prior stroke No New York Heart Association class II-IV heart disease No grade II-IV peripheral vascular disease within the past year No arterial thromboembolic event within the past 6 months, including any of the following: Unstable angina pectoris Myocardial infarction Transient ischemic attack Cerebrovascular accident No clinically significant peripheral artery disease No significant ophthalmologic abnormalities* including any of the following: Severe dry eye syndrome Keratoconjunctivitis sicca Sjögren's syndrome Severe exposure keratopathy Disorders that might increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior allergic reactions to compounds of similar chemical or biologic composition to bevacizumab or other study agents No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies No significant traumatic injury within the past 28 days No other concurrent uncontrolled illness No psychiatric illness or social situation that would preclude study compliance No ongoing or active infection requiring parenteral antibiotics No serious non-healing wound ulcer or bone fracture No seizures not controlled by standard medical therapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) More than 4 weeks since prior radiotherapy More than 4 weeks since prior major surgery More than 4 weeks since prior open biopsy Recovered from prior therapy No more than 1 prior regimen for recurrent disease No prior epidermal growth factor receptor (EGFR)-based therapy for recurrent disease No prior vascular EGFR-based therapy for recurrent disease No other concurrent investigational agents No other concurrent anticancer agents or therapies No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent chronic use of aspirin (325 mg/day or more) or other nonsteroidal anti-inflammatory drugs No concurrent warfarin or heparin, including low-molecular weight heparin No other concurrent or recent (within 1 month) thrombolytic agents or full-dose anticoagulants (except to maintain patency of preexisting, permanent indwelling IV catheters)

Sites / Locations

  • University of Chicago

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I

Arm II

Arm Description

Patients receive bevacizumab IV over 30-90 minutes on day 15 and oral erlotinib on days 1-28. All subsequent courses patients receive oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib on days 1-28. All subsequent courses patients receive oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Maximum tolerated dose of bevacizumab when used in combination with erlotinib hydrochloride determined by dose-limiting toxicities (Phase I)
Objective response rate (CR + PR) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II)
Progression-free survival rate (Phase II)
Overall survival rate (Phase II)

Secondary Outcome Measures

Full Information

First Posted
March 6, 2003
Last Updated
October 1, 2018
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00055913
Brief Title
Bevacizumab and Erlotinib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
Official Title
A Phase I/II Study Of Bevacizumab (rhuMAb VEGF) In Combination With OSI-774 For Patients With Recurrent Or Metastatic Cancer Of The Head And Neck
Study Type
Interventional

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
March 2003 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
This randomized phase I/II trial is to see if combining erlotinib with bevacizumab works better in treating patients who have recurrent or metastatic head and neck cancer. Erlotinib may stop the growth of tumor cells by blocking the enzymes needed for tumor cell growth. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. Combining erlotinib with bevacizumab may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose and dose-limiting toxicity of bevacizumab when administered with erlotinib in patients with recurrent or metastatic head and neck cancer. II. Determine the objective response rate and stable disease/absence of early progression in patients treated with this regimen. OUTLINE: This is a dose-escalation study of bevacizumab followed by a randomized, multicenter study. Phase I: Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Course 1 is 28 days in length. All subsequent courses are 21 days. Course 1: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 15 and oral erlotinib on days 1-28. Arm II: Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib on days 1-28. All subsequent courses: All patients receive bevacizumab as in arm II and oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Squamous Cell Carcinoma of the Hypopharynx, Recurrent Squamous Cell Carcinoma of the Larynx, Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity, Recurrent Squamous Cell Carcinoma of the Nasopharynx, Recurrent Squamous Cell Carcinoma of the Oropharynx, Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity, Salivary Gland Squamous Cell Carcinoma, 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, Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
58 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive bevacizumab IV over 30-90 minutes on day 15 and oral erlotinib on days 1-28. All subsequent courses patients receive oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Arm Title
Arm II
Arm Type
Experimental
Arm Description
Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral erlotinib on days 1-28. All subsequent courses patients receive oral erlotinib on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
bevacizumab
Other Intervention Name(s)
anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
erlotinib hydrochloride
Other Intervention Name(s)
CP-358,774, erlotinib, OSI-774
Intervention Description
Given orally
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Maximum tolerated dose of bevacizumab when used in combination with erlotinib hydrochloride determined by dose-limiting toxicities (Phase I)
Time Frame
28 days
Title
Objective response rate (CR + PR) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II)
Time Frame
Up to 6 months
Title
Progression-free survival rate (Phase II)
Time Frame
Time from the start of treatment until disease progression or death, assessed up to 7 years
Title
Overall survival rate (Phase II)
Time Frame
Up to 7 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed squamous cell cancer of the head and neck Recurrent or metastatic disease Determined to be incurable by surgery or radiotherapy Measurable disease No tumor involvement encasing or too close in proximity to a major artery or vein No known brain metastases No prior or concurrent CNS disease No primary brain tumor Performance status - ECOG 0-2 Performance status - Karnofsky 60-100% More than 12 weeks No history of bleeding diathesis WBC at least 3,000/mm^3 Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 INR less than 1.5 Bilirubin normal AST and ALT no greater than 2.5 times upper limit of normal Creatinine normal Creatinine clearance at least 60 mL/min No significant renal impairment 24-hour urinary protein less than 0.5 g required if more than trace proteinuria at baseline No uncontrolled hypertension No symptomatic congestive heart failure No serious cardiac arrhythmia requiring medication No deep venous thrombosis No prior stroke No New York Heart Association class II-IV heart disease No grade II-IV peripheral vascular disease within the past year No arterial thromboembolic event within the past 6 months, including any of the following: Unstable angina pectoris Myocardial infarction Transient ischemic attack Cerebrovascular accident No clinically significant peripheral artery disease No significant ophthalmologic abnormalities* including any of the following: Severe dry eye syndrome Keratoconjunctivitis sicca Sjögren's syndrome Severe exposure keratopathy Disorders that might increase the risk for epithelium-related complications (e.g., bullous keratopathy, aniridia, severe chemical burns, neutrophilic keratitis) Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior allergic reactions to compounds of similar chemical or biologic composition to bevacizumab or other study agents No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies No significant traumatic injury within the past 28 days No other concurrent uncontrolled illness No psychiatric illness or social situation that would preclude study compliance No ongoing or active infection requiring parenteral antibiotics No serious non-healing wound ulcer or bone fracture No seizures not controlled by standard medical therapy More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) More than 4 weeks since prior radiotherapy More than 4 weeks since prior major surgery More than 4 weeks since prior open biopsy Recovered from prior therapy No more than 1 prior regimen for recurrent disease No prior epidermal growth factor receptor (EGFR)-based therapy for recurrent disease No prior vascular EGFR-based therapy for recurrent disease No other concurrent investigational agents No other concurrent anticancer agents or therapies No concurrent combination antiretroviral therapy for HIV-positive patients No concurrent chronic use of aspirin (325 mg/day or more) or other nonsteroidal anti-inflammatory drugs No concurrent warfarin or heparin, including low-molecular weight heparin No other concurrent or recent (within 1 month) thrombolytic agents or full-dose anticoagulants (except to maintain patency of preexisting, permanent indwelling IV catheters)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tanguy Seiwert
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19201650
Citation
Cohen EE, Davis DW, Karrison TG, Seiwert TY, Wong SJ, Nattam S, Kozloff MF, Clark JI, Yan DH, Liu W, Pierce C, Dancey JE, Stenson K, Blair E, Dekker A, Vokes EE. Erlotinib and bevacizumab in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck: a phase I/II study. Lancet Oncol. 2009 Mar;10(3):247-57. doi: 10.1016/S1470-2045(09)70002-6. Epub 2009 Feb 7.
Results Reference
derived

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Bevacizumab and Erlotinib in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

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