Head and Neck Cancer
Conditions
Keywords
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 verrucous carcinoma of the larynx, stage IV squamous cell carcinoma of the larynx, stage IV verrucous carcinoma of the larynx, stage III squamous cell carcinoma of the lip and oral cavity, stage IV squamous cell carcinoma of the lip and oral cavity, stage III verrucous carcinoma of the oral cavity, stage IV verrucous carcinoma of the oral cavity, metastatic squamous neck cancer with occult primary squamous cell carcinoma, stage III squamous cell carcinoma of the nasopharynx, stage IV squamous cell carcinoma of the nasopharynx, stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx
Brief summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving erlotinib together with docetaxel and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well erlotinib given together with docetaxel and radiation therapy works in treating patients with stage III or stage IV squamous cell carcinoma of the head and neck.
Detailed description
OBJECTIVES: Primary * Determine the time to progression in patients with locally advanced squamous cell carcinoma of the head and neck treated with erlotinib hydrochloride in combination with docetaxel and radiotherapy. Secondary * Determine objective response rate, locoregional control rate, duration of response, patterns of failure, and overall survival in patients treated with this regimen. * Determine the toxicities of this regimen in these patients. * Determine the dose and effect of this treatment on biologic correlates in tumor tissue and/or surrounding mucosa. OUTLINE: This is a multicenter study. Patients receive oral erlotinib hydrochloride once daily for up to 2 years in the absence of disease progression or unacceptable toxicity. Beginning on week 3, patients receive docetaxel IV over 1 hour once a week and radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity. At 6-8 weeks after completion of chemoradiotherapy, patients with N2 or greater cervical lymph node involvement at baseline or with residual disease may undergo surgery. Patients with persistent disease during study therapy undergo salvage surgery 6-12 weeks after completion of chemoradiotherapy. Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR. After completion of study therapy, patients will be evaluated every 4-8 weeks for 1 year, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then once a year thereafter.
Interventions
DRUGdocetaxel
Beginning on week 3, patients receive docetaxel IV over 1 hour once a week
DRUGerlotinib hydrochloride
oral erlotinib hydrochloride once daily for up to 2 years in the absence of disease progression or unacceptable toxicity
GENETICfluorescence in situ hybridization
Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR.
GENETICpolymerase chain reaction
Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR.
OTHERimmunoenzyme technique
Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR.
OTHERimmunohistochemistry staining method
Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR.
OTHERlaboratory biomarker analysis
Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR.
OTHERpharmacological study
Patients undergo blood sample, tissue biopsy, mucosal scraping, and saliva collection at baseline and periodically during study. Samples are analyzed for markers of angiogenic activity (VEGF, sVEGFR-2, sKIT, ICAM, and PDGF), pharmacokinetic studies, gene expression profile, and human papilloma virus DNA by enzyme linked immunosorbent assay (ELISA), immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR.
PROCEDUREtherapeutic conventional surgery
At 6-8 weeks after completion of chemoradiotherapy, patients with N2 or greater cervical lymph node involvement at baseline or with residual disease may undergo surgery.Patients with persistent disease during study therapy undergo salvage surgery 6-12 weeks after completion of chemoradiotherapy.
RADIATIONintensity-modulated radiation therapy
radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.
RADIATIONradiation therapy
radiotherapy (may be intensity-modulated) once daily for 8 weeks in the absence of disease progression or unacceptable toxicity.
Sponsors
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed locally advanced squamous cell carcinoma of the head and neck * Stage III or IV disease * No distant metastatic disease * Measurable disease (according to RECIST) * No salivary gland and paranasal sinus squamous cell carcinoma * No known brain metastases or direct cerebral invasion by tumor * Intracranial extension (without cerebral involvement) may be allowed PATIENT CHARACTERISTICS: * ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100% * Life expectancy \> 12 weeks * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥10 g/dL * Total bilirubin normal * Alkaline phosphatase AND AST and ALT meeting the following criteria: * Alkaline phosphatase normal AND AST and ALT ≤ 5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 2.5 times ULN AND AST and ALT ≤ 2.5 times ULN * Alkaline phosphatase ≤ 5 times ULN AND AST and ALT normal * Creatinine normal OR creatinine clearance ≥ 60 mL/min * No clinically significant heart disease including any of the following: * NYHA class III or IV heart disease * Significant arrhythmias requiring medication * Symptomatic coronary artery disease * Myocardial infarction within the previous six months * Second- or third-degree heart block or bundle-branch block * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for at least 3 months after completion of study therapy * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride or docetaxel, including other drugs formulated with polysorbate 80 * No pre-existing peripheral neuropathy ≥ grade 2 * No uncontrolled concurrent illness including, but not limited to, any of the following: * Ongoing or active infection * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia * Psychiatric illness/social situations that would preclude compliance with study requirements * No HIV positivity * No other prior malignancy except for any of the following: * Squamous cell or basal cell carcinoma of the skin * Carcinoma in situ of the cervix * Cancer that was treated more than 5 years ago and the patient has remained disease-free * Not poorly compliant PRIOR CONCURRENT THERAPY: * No prior chemotherapy, radiotherapy, or investigational antitumor drug * No other concurrent investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression (TTP) | 3 yrs after treatment | Time from start of treatment to first documented occurrence of progressive disease (PD). PD defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. |
| Percent of Participants With Disease-Free Survival (DFS) at 3 Years | 3 yrs after treatment | Percent of participants with Disease-Free survival (DFS) at 3 years. Assessed from date of treatment to date of death or date of disease progression, and to date of last follow-up for those still alive and progression free. Disease-free Survival percentages were calculated using Kaplan-Meier estimates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 3 years | Percent of participants alive at follow-up time. Overall survival time is evaluated from the date of treatment to date of death, and to date of last follow-up for those still alive. |
| Number of Participants With Acute Grade III/IV Treatment-related Toxicities | evaluated every 2 weeks, up to 3 years | Number of participants with acute grade III/IV treatment-related toxicities |
| Percent of Participants With Local Failure-free Survival | At 3 years | Participants with Local absence of relapse or recurrence or progression within the prescribed radiation field. |
| Percent of Participants With Locoregional Failure-free Survival | At 3 years | Participants with the locoregional absence of relapse or recurrence or progression within the prescribed radiation field. Locoregional failure-free survival percentages were calculated using Kaplan-Meier estimates. |
| Percent of Participants With Distant Metastasis-free Survival | At 3 years | Percent of participants with distant metastasis-free survival |
| Percent of Participants With Regional Failure-free Survival | At 3 years | Participants with the regional absence of relapse or recurrence or progression within the prescribed radiation field. Failure-free Survival percentages were calculated using Kaplan-Meier estimates. |
| Response Rate (Complete Response, Partial Response, Stable Disease, and Disease Progression) | 3 yrs after treatment | Response rate according to response criteria, which defines the following: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions |
Other
| Measure | Time frame |
|---|---|
| Predictive Values of EGFR/TGF-α, VEGF | collection at baseline and periodically during study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CASE5307 - Oral Erlotinib Hydrochloride Docetaxel, erlotinib hydrochloride, fluorescence in situ hybridization, polymerase chain reaction, immunoenzyme technique, immunohistochemistry staining method, laboratory biomarker analysis, pharmacological study, therapeutic conventional surgery, intensity-modulated radiation therapy, radiation therapy | 37 |
| Participants From CWRU1301 Participants from CWRU1301 - NCT00049283 who received Docetaxel 20 mg/m2/wk Erlotinib 150 mg/day XRT | 6 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Disease progression | 6 | 1 |
| Overall Study | Physician Decision | 5 | 2 |
| Overall Study | Withdrawal by Subject | 14 | 1 |
Baseline characteristics
| Characteristic | Participants From CWRU1301 | Total | CASE5307 - Oral Erlotinib Hydrochloride |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 12 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 31 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 40 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 6 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 35 Participants | 32 Participants |
| Region of Enrollment United States | 6 participants | 43 participants | 37 participants |
| Sex: Female, Male Female | 1 Participants | 10 Participants | 9 Participants |
| Sex: Female, Male Male | 5 Participants | 33 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 37 | 4 / 6 |
| other Total, other adverse events | 33 / 37 | 6 / 6 |
| serious Total, serious adverse events | 11 / 37 | 1 / 6 |
Outcome results
Primary
Percent of Participants With Disease-Free Survival (DFS) at 3 Years
Percent of participants with Disease-Free survival (DFS) at 3 years. Assessed from date of treatment to date of death or date of disease progression, and to date of last follow-up for those still alive and progression free. Disease-free Survival percentages were calculated using Kaplan-Meier estimates.
Time frame: 3 yrs after treatment
Population: Participants enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Erlotinib Hydrochloride | Percent of Participants With Disease-Free Survival (DFS) at 3 Years | 69.5 Percent |
Primary
Time to Progression (TTP)
Time from start of treatment to first documented occurrence of progressive disease (PD). PD defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: 3 yrs after treatment
Population: Data not available because response data not collected
Secondary
Number of Participants With Acute Grade III/IV Treatment-related Toxicities
Number of participants with acute grade III/IV treatment-related toxicities
Time frame: evaluated every 2 weeks, up to 3 years
Population: Participants enrolled in study
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Oral Erlotinib Hydrochloride | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | Grade 3 | 24 Participants |
| Oral Erlotinib Hydrochloride | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | grade 4 | 17 Participants |
| Neutropenia | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | Grade 3 | 2 Participants |
| Neutropenia | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | grade 4 | 0 Participants |
| Anemia | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | Grade 3 | 3 Participants |
| Anemia | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | grade 4 | 0 Participants |
| Oral Mucositis | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | Grade 3 | 14 Participants |
| Oral Mucositis | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | grade 4 | 1 Participants |
| Radiation Dermatitis | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | grade 4 | 1 Participants |
| Radiation Dermatitis | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | Grade 3 | 15 Participants |
| Acneiform Skin Rash | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | grade 4 | 0 Participants |
| Acneiform Skin Rash | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | Grade 3 | 4 Participants |
| Dysphagia | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | grade 4 | 1 Participants |
| Dysphagia | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | Grade 3 | 20 Participants |
| Anorexia | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | Grade 3 | 13 Participants |
| Anorexia | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | grade 4 | 0 Participants |
| Nausia/Vomiting | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | Grade 3 | 7 Participants |
| Nausia/Vomiting | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | grade 4 | 0 Participants |
| Dehydration | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | Grade 3 | 2 Participants |
| Dehydration | Number of Participants With Acute Grade III/IV Treatment-related Toxicities | grade 4 | 0 Participants |
Secondary
Overall Survival (OS)
Percent of participants alive at follow-up time. Overall survival time is evaluated from the date of treatment to date of death, and to date of last follow-up for those still alive.
Time frame: 3 years
Population: Participants enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Erlotinib Hydrochloride | Overall Survival (OS) | 81 Percent |
Secondary
Percent of Participants With Distant Metastasis-free Survival
Percent of participants with distant metastasis-free survival
Time frame: At 3 years
Population: Participants enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Erlotinib Hydrochloride | Percent of Participants With Distant Metastasis-free Survival | 83.7 percent |
Secondary
Percent of Participants With Local Failure-free Survival
Participants with Local absence of relapse or recurrence or progression within the prescribed radiation field.
Time frame: At 3 years
Population: Participants enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Erlotinib Hydrochloride | Percent of Participants With Local Failure-free Survival | 90 percent |
Secondary
Percent of Participants With Locoregional Failure-free Survival
Participants with the locoregional absence of relapse or recurrence or progression within the prescribed radiation field. Locoregional failure-free survival percentages were calculated using Kaplan-Meier estimates.
Time frame: At 3 years
Population: Participants enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Erlotinib Hydrochloride | Percent of Participants With Locoregional Failure-free Survival | 82.4 percent (Kaplan-Meier estimates) |
Secondary
Percent of Participants With Regional Failure-free Survival
Participants with the regional absence of relapse or recurrence or progression within the prescribed radiation field. Failure-free Survival percentages were calculated using Kaplan-Meier estimates.
Time frame: At 3 years
Population: Participants enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oral Erlotinib Hydrochloride | Percent of Participants With Regional Failure-free Survival | 87.1 percent (Kaplan-Meier estimates) |
Secondary
Response Rate (Complete Response, Partial Response, Stable Disease, and Disease Progression)
Response rate according to response criteria, which defines the following: Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
Time frame: 3 yrs after treatment
Population: Data not available because response data not collected
Other Pre-specified
Predictive Values of EGFR/TGF-α, VEGF
Time frame: collection at baseline and periodically during study.