Cancer of Head and Neck
Conditions
Keywords
Head and Neck Neoplasms
Brief summary
The purpose of this study is to evaluate the response of the tumor to the treatment regimen that will be used in this study. This study will also test the safety of cetuximab (C225), given with chemotherapy and radiation therapy. We also want to see what effects (good and bad) cetuximab, chemotherapy, and radiation therapy have head & neck cancer. C225 has been designed to stop the growth of the tumor by blocking certain chemical pathways that lead to tumor cell growth. In prior studies with head & neck cancer patients, C225 has delayed tumor growth and provided relief of symptoms in some patients.
Detailed description
Primary Objective- To evaluate whether the addition of Cetuximab (C225) in combination with chemotherapy and radiation can cause an enhanced anti-tumor effect resulting in improving local regional control of patients with locally advanced, unresectable squamous cell carcinoma of head and neck. (SCCHN). OVERVIEW OF STUDY DESIGN Open label, non-randomized, single arm trial. P = Paclitaxel will be administered on a weekly schedule at a dose of 40mg/m2 IV by 1-hour infusion prior to cetuximab dose. This will be administered for a total of 8 weeks (from weeks 2-9) C225 = Cetuximab: 400 mg/m2 IV will be given as the initial OR loading dose in week 1 and then 250 mg/m2 IV weekly will be given for 8 weeks (weeks 2-9). C = Carboplatin will be given at a dose of AUC=2/week - will be administered as a 30 minute infusion after cetuximab infusion (weeks 2-9) RT = Radiation therapy will be delivered at 1.8 Gy fraction/day, 5 days a week for a total of 70.2 Gy. RT will be given from weeks 2-9. Note: Sequence of administration will be paclitaxel followed by cetuximab followed by carboplatin followed by XRT. Approximately 60 patients from MSGCC/BVAMC will participate in this study. Prior to entering the study the doctor will examine the patient and order blood tests ( which will be done by blood draw, approximately 2 tablespoons) and tests to measure the patients disease (scans). The patient will also be evaluated by a dietician who will follow the patient throughout the course of the therapy to help the patient meet his/her nutritional needs
Interventions
DRUGErbitux, Paclitaxel & Carboplatin
Paclitaxel, 40 mg/m2/week, 1-hour infusion (weeks 2-9.Paclitaxel will be administered on a weekly schedule at a dose of 40mg/m2 IV by 1-hour infusion prior to cetuximab dose. Cetuximab: 400 mg/m2 IV (initial dose) week 1 then 250 mg/m2 IV weekly for 8 weeks weeks 2-9). Cetuximab will be administered 400mg/m2 IV on Day 1, then the first 250 mg/m2 IV dose will be given on day 8 (week 2) prior to carboplatin dose. Carboplatin, AUC=2/week as a 30 minute infusion after cetuximab infusion (weeks 2-9)Carboplatin will be administered at a dose of AUC = 2/week IV bolus each week and will be administered prior to head and neck irradiation dose. (Carboplatin: AUC=2/week x 8 weeks (weeks 2-9)
RADIATIONRadiation
XRT=Radiotherapy 1.8 Gy radiation/day, 5 days a week for a total of 70.2 Gy.(weeks 2-9) - IMRT is allowed
Sponsors
University of Maryland, Baltimore
Bristol-Myers Squibb
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
1. Histologically proved locally advanced squamous cell carcinoma of the head and neck of all primary sites. The following TNM stages by sites will be eligible.Oral cavity, Pharynx, Larynx, Nasopharynx, paranasal sinuses, Oral cavity, Pharynx, Larynx, Nasopharynx, paranasal sinuses- T4 N0 N1 N2-A,B,C N3, T3 N0 N1 N2-A,B,C N3 Any T N2-A,B,C N3 Unknown primary Tx N2-A,B,C N3 Note: Only clearly unresectable T4 N0 lesions are eligible for study provided the reasons for unresectability are due to extensive anatomic involvement and are outlined by the surgeon 2. Patients must have signed an approved informed consent. 3. Patients with Performance Status 0-2. 4. No evidence of distant metastatic disease. 5. No previous radiation therapy. 6. No previous chemotherapy. 7. Patients must be greater than 18 years of age. 8. Women of child bearing potential (WOCBP) must have a negative pregnancy test within 7 days of treatment. Patients are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. 9. Pretreatment evaluations include: History and physical examination within four weeks prior to study entry Dental evaluation Medical oncology examination to evaluate medical contraindications prior to start of chemotherapy 10. Adequate renal & bone marrow function determined by the following laboratory parameters: ANC greater than or equal to 1500/mm3; platelets greater than or equal to 100,000/mm3; hemoglobin greater than or equal to 8.0 g/dl; Serum Creatinine less than or equal to 2.0 mg/dl, Total bilirubin less than 1.5 X the ULIN; AST/ALT less than 3 times the ULN, Creatinine Clearance greater than or equal to 50 cc/min 11. Evidence of measurable disease. 12. No evidence of concomitant malignancy except for non-melanomatous skin cancer (controlled or controllable) or carcinoma in situ of the cervix.
Exclusion criteria
Any of the following criteria will make the patient ineligible to participate in this study: 1. Acute hepatitis or known HIV. 2. Active or uncontrolled infection. 3. Significant history of concomitant life threatening / uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and known cardiomyopathy with decreased ejection fraction, cardiac arrhythmia 4. Prior therapy which specifically and directly targets the EGFR pathway. 5. Prior severe infusion reaction to a monoclonal antibody. 6. Any concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s). 7. Women of childbearing potential (WOCBP) and male participants who are unwilling or unable to use an effective method to avoid pregnancy for the entire study period 8. Preexisting clinically significant neuropathy. 9. Patients with loco-regional recurrences from any site with no prior radiation therapy and not amenable for salvage surgery are not eligible for study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Endpoint is the Local Regional Control Rate Assessed 3 Months Post Completion of Radiation Therapy. | 3 months | The local regional control rate was assessed 3 months post completion of radiation therapy based on either MRI or CT and clinical exam. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local Regional Control at 2 Years | 2 years | — |
| Overall Survival and Disease-free Survival | 3 years (overall) 2 years disease-free | — |
| Pathological Response to Cetuximab | 2 years | Adding CTX to weekly PC and daily RT. CBC and Chemistry panel blood testing |
| Percentage of Participants With Grade 3 Toxicities of Cetuximab | 9 weeks | One of the more serious side effects of cetuximab therapy is the incidence of acne-like rash. This rash rarely leads to dose reductions or termination of therapy. It is generally reversible. Further severe infusion reactions include but are not limited to: fevers, chills, rigors, urticaria, pruritis, rash, hypotension, N/V, HA, bronchospasm, dyspnea, wheezing, angioedema, dizziness, anaphylaxis, and cardiac arrest. Therefore, pretreatment with diphenhydramine 30-60 min. before administration is standard of care. Other common side effects include photosensitivity, hypomagnesemia due to magnesium wasting, and less commonly pulmonary and cardiac toxicity. |
| Clinical Complete Response Rate of This Regimen in the Population | 3 months | What is the the complete response (CR) rate at the completion of therapy. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cetuximab (ERBITUX) and Concurrent Carboplatin | 43 |
| Total | 43 |
Baseline characteristics
| Characteristic | Cetuximab (ERBITUX) and Concurrent Carboplatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Region of Enrollment United States | 43 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 43 |
| serious Total, serious adverse events | 3 / 43 |
Outcome results
Primary
The Primary Endpoint is the Local Regional Control Rate Assessed 3 Months Post Completion of Radiation Therapy.
The local regional control rate was assessed 3 months post completion of radiation therapy based on either MRI or CT and clinical exam.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concurrent Chemo Raditaion Wtih Cetuximab | The Primary Endpoint is the Local Regional Control Rate Assessed 3 Months Post Completion of Radiation Therapy. | 43 participants |
Secondary
Clinical Complete Response Rate of This Regimen in the Population
What is the the complete response (CR) rate at the completion of therapy.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Concurrent Chemo Raditaion Wtih Cetuximab | Clinical Complete Response Rate of This Regimen in the Population | 84 percentage of participants | 38 |
Secondary
Local Regional Control at 2 Years
Time frame: 2 years
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Concurrent Chemo Raditaion Wtih Cetuximab | Local Regional Control at 2 Years | 72 percentage of participants | 38 |
Secondary
Overall Survival and Disease-free Survival
Time frame: 3 years (overall) 2 years disease-free
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Concurrent Chemo Raditaion Wtih Cetuximab | Overall Survival and Disease-free Survival | overall survival | 59 percentage of participants | 38 |
| Concurrent Chemo Raditaion Wtih Cetuximab | Overall Survival and Disease-free Survival | disease-free survival | 58 percentage of participants | — |
Secondary
Pathological Response to Cetuximab
Adding CTX to weekly PC and daily RT. CBC and Chemistry panel blood testing
Time frame: 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concurrent Chemo Raditaion Wtih Cetuximab | Pathological Response to Cetuximab | 43 participants |
Secondary
Percentage of Participants With Grade 3 Toxicities of Cetuximab
One of the more serious side effects of cetuximab therapy is the incidence of acne-like rash. This rash rarely leads to dose reductions or termination of therapy. It is generally reversible. Further severe infusion reactions include but are not limited to: fevers, chills, rigors, urticaria, pruritis, rash, hypotension, N/V, HA, bronchospasm, dyspnea, wheezing, angioedema, dizziness, anaphylaxis, and cardiac arrest. Therefore, pretreatment with diphenhydramine 30-60 min. before administration is standard of care. Other common side effects include photosensitivity, hypomagnesemia due to magnesium wasting, and less commonly pulmonary and cardiac toxicity.
Time frame: 9 weeks
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Concurrent Chemo Raditaion Wtih Cetuximab | Percentage of Participants With Grade 3 Toxicities of Cetuximab | mucositis | 79 percentage of participants | 43 |
| Concurrent Chemo Raditaion Wtih Cetuximab | Percentage of Participants With Grade 3 Toxicities of Cetuximab | rash | 9 percentage of participants | — |
| Concurrent Chemo Raditaion Wtih Cetuximab | Percentage of Participants With Grade 3 Toxicities of Cetuximab | leukopenia | 19 percentage of participants | — |
| Concurrent Chemo Raditaion Wtih Cetuximab | Percentage of Participants With Grade 3 Toxicities of Cetuximab | neutropenia | 19 percentage of participants | — |
| Concurrent Chemo Raditaion Wtih Cetuximab | Percentage of Participants With Grade 3 Toxicities of Cetuximab | RT dermatisis | 16 percentage of participants | — |