Evaluation of Cetuximab (ERBITUX) and Concurrent Carboplatin, Paclitaxel & Radiotherapy in the Management of Patients With Advanced Locoregional Squamous Cell Carcinomas of the Head and Neck (GCC 0442)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00343083
Recruitment Status : Completed
First Posted : June 22, 2006
Results First Posted : April 9, 2014
Last Update Posted : March 16, 2016
Bristol-Myers Squibb
Information provided by (Responsible Party):
Department of Radiation Oncology, University of Maryland

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.

Condition or disease Intervention/treatment Phase
Cancer of Head and Neck Drug: Erbitux, Paclitaxel & Carboplatin Radiation: Radiation Phase 2

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Evaluation of Cetuximab (ERBITUX) and Concurrent Carboplatin, Paclitaxel & Radiotherapy in the Management of Patients With Advanced Locoregional Squamous Cell Carcinomas of the Head and Neck
Study Start Date : December 2004
Actual Primary Completion Date : June 2011
Actual Study Completion Date : May 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: Cetuximab comparison for Head and Neck Cancer

To report the mature data of a prospective Phase II trial designed to evaluate the efficacy of an epidermal growth factor receptor inhibitor cetuximab (CTX) added to the concurrent therapy of weekly paclitaxel/carboplatin (PC) and daily radiation therapy (RT).

Both chemotherapy and radiation will be given on a weekly basis (see interventions for details).

Drug: Erbitux, 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)

Other Name: Taxol, Erbitux
Radiation: Radiation
XRT=Radiotherapy 1.8 Gy radiation/day, 5 days a week for a total of 70.2 Gy.(weeks 2-9) - IMRT is allowed

Primary Outcome Measures :
  1. The Primary Endpoint is the Local Regional Control Rate Assessed 3 Months Post Completion of Radiation Therapy. [ Time Frame: 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 Outcome Measures :
  1. Local Regional Control at 2 Years [ Time Frame: 2 years ]
  2. Overall Survival and Disease-free Survival [ Time Frame: 3 years (overall) 2 years disease-free ]
  3. Pathological Response to Cetuximab [ Time Frame: 2 years ]
    Adding CTX to weekly PC and daily RT. CBC and Chemistry panel blood testing

  4. Percentage of Participants With Grade 3 Toxicities of Cetuximab [ Time Frame: 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.

  5. Clinical Complete Response Rate of This Regimen in the Population [ Time Frame: 3 months ]
    What is the the complete response (CR) rate at the completion of therapy.

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00343083

United States, Maryland
University of Maryland & Baltimore VA medical centre
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
Department of Radiation Oncology
Bristol-Myers Squibb
Principal Investigator: Mohan Suntharalingam, M.D University of Maryland

Responsible Party: Department of Radiation Oncology, Principal Investigator, University of Maryland Identifier: NCT00343083     History of Changes
Other Study ID Numbers: HP-00042712
First Posted: June 22, 2006    Key Record Dates
Results First Posted: April 9, 2014
Last Update Posted: March 16, 2016
Last Verified: February 2016

Keywords provided by Department of Radiation Oncology, University of Maryland:
Head and Neck Neoplasms

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Neoplasms by Site
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action