Cancer of the Larynx, Cancer of the Oral Cavity, Cancer of the Pharynx, Head and Neck Cancer, Nose Neoplasms, Paranasal Sinus Neoplasms
Conditions
Keywords
Cancer of the Nasal Cavity
Brief summary
For advanced head and neck cancer, combined radiation and chemotherapy prevents recurrences and for many patients, improves survival. While combined cisplatin and radiation or cetuximab and radiation is more effective than radiation alone, approximately 50% of these patients will still recur. A more aggressive approach may be needed for these patients to prevent recurrence and death. The strategy of using multiple chemotherapy drugs with radiation given twice a day has been tested at Mount Sinai and University of Chicago. Approximately 80% of patients are cured with this strategy. While cure rates are higher than standard chemotherapy and radiation and the treatment is tolerable, side effects during treatment are common. We propose replacing a chemotherapy drug with a less toxic, targeted therapy called cetuximab. Our goal is to reduce toxicity while maintaining or improving cure rates for these patients.
Interventions
DRUGCetuximab
250 mg/m2 on Day 1 after the first dose of radiation was administered to all patients
DRUGHydroxyurea
500 mg orally every 12 hours with the morning dose administered 2 hours before radiation
DRUGFluorouracil
continuous-infusion 5-FU at a dose of 600 mg/m2 daily for 120 hours
PROCEDUREradiotherapy
Radiotherapy was administered at 1.5 Gy per fraction twice daily with treatments separated by at least 6 hours on Days 1 through 5 on an alternating week schedule. Radiation was delivered with intensity-modulated radiation therapy (IMRT) planning for all patients.
Sponsors
Johnny Kao
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
* Age 18 years or older * Histologically or cytologically confirmed diagnosis of squamous cell or poorly differentiated carcinomas of the head and neck or lymphoepithelioma * No prior chemotherapy or radiotherapy * Prior surgical therapy will consist only of incisional or excisional biopsy, and organ sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an existing primary tumor * Karnofsky performance status of \>= 70% * Intact organ and bone marrow function * Obtained informed consent
Exclusion criteria
* Demonstration of metastatic disease (i.e. M1 disease). * Patients with a history of severe allergic reaction to docetaxel or other drugs formulated with polysorbate 80. History of allergic reactions attributed to compounds of similar chemical or biologic composition to cisplatin, 5-fluorouracil, or hydroxyurea. * Other coexisting malignancies or malignancies diagnosed within the previous 3 years with the exception of basal cell carcinoma, cervical cancer in situ, and other treated malignancies with no evidence of disease for at least 3 years. * Prior surgical therapy other than incisional or excisional biopsy and organ-sparing procedures such as debulking of airway-compromising tumors or neck dissection in a patient with an unknown primary tumor. Any non-biopsy procedure must have taken place less than 3 months from initiating protocol treatment. * Incomplete healing from previous surgery * Pregnancy or breast feeding (men and women of child-bearing potential are eligible but must consent to using effective contraception during therapy and for at least 3 months after completing therapy) * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF are excluded. The exclusion of patients with active coronary artery disease will be at the discretion of the attending physician. * Uncontrolled active infection unless curable with treatment of their cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Llocoregional Recurrence | 2 years | Percentage of Participants with Loco-regional recurrence. |
| Survival | 2 years | Overall Survival - Percentage of Participants who survived Disease-Free Survival - measured from the initiation of nonsurgical treatment to either the last follow-up, disease progression, or death using intent-to-treat methodology |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Long- Term Toxicity | 2 years | Grade 3 toxicities events |
| UW-QOLR: Quality of Life Score | 2 years | University of Washington Quality of Life (UW-QOLR) questionnaire - covers 12 domains - pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder function, taste, saliva, mood and anxiety. Each domain have between 3 and 6 response options that are scaled evenly from 0 (worst) to 100 (best) according to the hierarchy of response and reported as one composite score from 0 (worst) to 100 (best). |
| Distant Metastases | 2 years | Percentage of participants who did not have distant control |
Countries
United States
Participant flow
Recruitment details
Recruitment period January 2007 through April 2008. All cases were reviewed at a multidisciplinary conference, which was attended by representatives from the Departments of Head and Neck Surgery, Radiation Oncology, Medical Oncology, Palliative Care, Social Work, and Nutrition at Icahn School of Medicine at Mount Sinai.
Participants by arm
| Arm | Count |
|---|---|
| Advanced Head and Neck Cancer Cetuximab- 250 mg/m2 on Day 1 after the first dose of radiation was administered to all patients. Hydroxyurea - 500 mg orally every 12 hours with the morning dose administered 2 hours before radiation. Fluorouracil - continuous-infusion 5-FU at a dose of 600 mg/m2 daily for 120 hours. Radiotherapy. | 33 |
| Total | 33 |
Baseline characteristics
| Characteristic | Advanced Head and Neck Cancer |
|---|---|
| Age, Continuous | 59 years |
| Alcohol consumption Heavy | 7 participants |
| Alcohol consumption Moderate | 2 participants |
| Alcohol consumption None | 10 participants |
| Alcohol consumption Occasional | 14 participants |
| Charlson comorbidity score 0-1 | 27 participants |
| Charlson comorbidity score ≥2 | 6 participants |
| Performance score 0 | 12 participants |
| Performance score 1 | 19 participants |
| Performance score 2 | 2 participants |
| Primary site Hyopharynx | 4 participants |
| Primary site Larynx | 2 participants |
| Primary site Nasopharynx | 2 participants |
| Primary site Oral cavity | 6 participants |
| Primary site Oropharynx | 14 participants |
| Primary site Salivary gland | 1 participants |
| Primary site Sinonasal | 2 participants |
| Primary site Unknown primary | 2 participants |
| Race/Ethnicity, Customized Asian | 0 participants |
| Race/Ethnicity, Customized Black | 5 participants |
| Race/Ethnicity, Customized Hispanic | 5 participants |
| Race/Ethnicity, Customized White | 23 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 24 Participants |
| Smoking 20.1-40 packk-y | 7 participants |
| Smoking ≤20 pack-y | 9 participants |
| Smoking >40 pack-y | 8 participants |
| Smoking Cigar, pipe, or betel nut only | 3 participants |
| Smoking None | 6 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 33 / 33 |
Outcome results
Primary
Llocoregional Recurrence
Percentage of Participants with Loco-regional recurrence.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Advanced Head and Neck Cancer | Llocoregional Recurrence | 27 Participants |
Primary
Survival
Overall Survival - Percentage of Participants who survived Disease-Free Survival - measured from the initiation of nonsurgical treatment to either the last follow-up, disease progression, or death using intent-to-treat methodology
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Advanced Head and Neck Cancer | Survival | Overall Survival | 86 percentage of participants |
| Advanced Head and Neck Cancer | Survival | Disease-Free Survival | 69 percentage of participants |
Secondary
Distant Metastases
Percentage of participants who did not have distant control
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Advanced Head and Neck Cancer | Distant Metastases | 21 percentage of participants |
Secondary
Long- Term Toxicity
Grade 3 toxicities events
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Advanced Head and Neck Cancer | Long- Term Toxicity | 32 events |
Secondary
UW-QOLR: Quality of Life Score
University of Washington Quality of Life (UW-QOLR) questionnaire - covers 12 domains - pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder function, taste, saliva, mood and anxiety. Each domain have between 3 and 6 response options that are scaled evenly from 0 (worst) to 100 (best) according to the hierarchy of response and reported as one composite score from 0 (worst) to 100 (best).
Time frame: 2 years
Population: Twenty patients completed the UW-QOLR questionnaire before and after therapy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Advanced Head and Neck Cancer | UW-QOLR: Quality of Life Score | 80 units on a scale |