Radiation Therapy and Bortezomib and Cetuximab With or Without Cisplatin to Treat Head and Neck Cancer

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01445405
First received: September 30, 2011
Last updated: October 23, 2014
Last verified: February 2013
  Purpose

Background:

Bortezomib acts on molecules in head and neck cancer cells that are important for the cells growth and survival. The drug may help make the cancer more sensitive to radiation and other chemotherapy drugs.

Cetuximab is a monoclonal antibody that has increased the effectiveness of radiation treatment in patients with head and neck cancer in clinical trials.

Cisplatin has shrunk head and neck cancers and improved treatment response and survival when combined with radiation treatment.

Objectives:

To determine the highest safe dose of bortezomib when combined with cetuximab without or with cisplatin and with radiation in patients with advanced head and neck cancer.

To examine the benefits and side effects of these drug combinations with radiation in patients with advanced head and neck cancer.

Eligibility:

Patients 18 years of age and older with advanced Stage IV head and neck cancer who have not previously had neck radiation.

Design:

Patients will be assigned sequentially to one of two treatment groups: Group A receives bortezomib and cetuximab beginning the week before, and for the duration of, radiation therapy; Group B receives bortezomib, cetuximab and cisplatin beginning the week before, and for the duration of, radiation therapy.

  • Cetuximab is given as a 2-hour infusion through a vein (intravenously, IV) for the first dose and then over 1 hour for subsequent weekly doses.
  • Bortezomib is given as an injection into a vein over about 5 seconds, twice a week for 2 weeks, followed by a 1-week rest for a total of three 3-week treatment cycles during radiation.
  • Cisplatin is given in once a week as a 1-hour IV infusion
  • Radiation therapy is given 5 days a week for 7 to 8 weeks.

Post-treatment follow-up:

  • Until 2 weeks after treatment ends, patients are followed once a week including a physical examination, review of treatment side effects, and blood tests.
  • For 2 months after treatment ends, patients may need to return to the hospital for medical evaluation and supportive care, depending on their condition.
  • 8-weeks after treatment ends, patients return for evaluation with a history and physical examination; blood tests; ear, nose and throat evaluation and endoscopy; CT or MRI scan, or both, of the neck and chest; and, if indicated, a PET scan....

Condition Intervention Phase
Carcinoma, Squamous
Head and Neck Cancer
Oral Cancer
Laryngeal Cancer
Pharyngeal Cancer
Drug: Bortezomib (Velcade, PS-341)
Drug: Cetuximab
Drug: Cisplatin
Procedure: Radiation Therapy
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Bortezomib and Cetuximab Without or With Cisplatin in Combination With Radiation Therapy for Advanced Head and Neck Cancer

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Evaluate feasibility/toxicities of combining proteasome inhibitor bortezomib with cetuximab without/with cisplatin concurrent with radiation for therapy of Pts with advanced SCCHN, and identify MTD for bortezomib for further clinical phase 2 dev...

Secondary Outcome Measures:
  • 1) Evaluate objective response rate, progression-free survival/overall survival with the above regimen. 2) Determine effects of bortezomib with cetuximab or with cetuximab/ cisplatin to inhibit activation of NF-kB, EGFR, MAPK, and STAT3 signal p...

Enrollment: 3
Study Start Date: February 2008
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Bortezomib (Velcade, PS-341)
    N/A
    Drug: Cetuximab
    N/A
    Drug: Cisplatin
    N/A
    Procedure: Radiation Therapy
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA:

  1. Histologically or cytologically confirmed squamous cell carcinoma, including variants, or undifferentiated/poorly differentiated carcinoma of the head and neck (any site, except nasopharynx).
  2. Previously untreated stage IV disease (AJCC staging system, 6th edition), or,
  3. Patients with residual disease or regional recurrence of head and neck cancer after surgery and/or chemotherapy, but with no prior bortezomib, EGFR inhibitor therapy or head and neck radiotherapy. All such patients should be eligible to receive full dose radiation therapy, and must be evaluated and accepted for treatment by a Radiation Oncologist. Prior cisplatin is allowed if administered greater than 3 months earlier.
  4. Patients with no clinically measurable distant disease, or those with asymptomatic small distant lesions outside the radiation field of less than or equal to 3cm individual or aggregate diameter, but for whom palliation of local and regional disease is clinically warranted will be eligible.
  5. Any number of other prior systemic therapies is allowed. Patients must have fully recovered from the effects of any prior surgery, or chemotherapy. A minimum time period of 4 weeks (6 weeks for nitrosoureas or mitomycin C) should elapse between the completion of prior chemotherapy and enrollment in the study.
  6. Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of bortezomib in combination with cetuximab or cisplatin and radiation in patients < 18 years of age, and head and neck cancer in children is exceedingly rare, except for those with disorders of DNA damage repair, bone marrow or transplant immunosuppression likely to have lower tolerance to these drugs and RT, children are excluded from this study.
  7. ECOG performance status 0-1 (Karnofsky greater than or equal to 70 percent).
  8. Patients must have normal organ and marrow function as defined below:

    • absolute neutrophil count greater than or equal to 1,500/mcL
    • platelets greater than or equal to 100,000/mcL
    • total bilirubin within normal institutional limits, except for patients with Gilberts syndrome, with increased indirect bilirubin less than or equal to 3 mg/dL
    • AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times institutional upper limit of normal
    • creatinine within normal institutional limits

    OR

    -creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with creatinine levels above institutional normal.

  9. The effects of bortezomib on the developing human fetus are unknown. For this reason and because other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must have agreed to use adequate contraception (hormonal or barrier method of birth control; prior vasectomy; tubal ligation or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  10. Adequate cognitive and neurologic function to protect against and detect and report toxicities experienced, and to understand and to sign a written informed consent document.

EXCLUSION CRITERIA:

  1. Patients with previously untreated nasopharyngeal cancer (any stage) will be excluded, but patients with recurrent nasopharyngeal carcinoma will be eligible.
  2. Prior treatment with radiation to the head and neck, or systemic EGFR inhibitors or bortezomib is not allowed.
  3. Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  4. Patients may not be receiving any other investigational agents.
  5. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  6. History of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib, cetuximab, cisplatin or other agents used in study.
  7. Patients with greater than or equal to grade 2 peripheral sensory neuropathy because bortezomib can cause irreversible worsening and a painful type of chemotherapy associated peripheral neuropathy.
  8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  9. Pregnant women are excluded from this study because bortezomib, cetuximab and cisplatin have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with bortezomib, cetuximab and cisplatin, breastfeeding should be discontinued if the mother is treated with bortezomib, cetuximab and cisplatin. These potential risks may also apply to other agents used in this study.
  10. HIV-positive patients or patients on any antiretroviral therapy are ineligible because of the potential for possible pharmacodynamic interactions with bortezomib, cetuximab and cisplatin, particularly bone marrow and mucosal toxicity, which could affect the MTD. These patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01445405

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Carter Van Waes, M.D. National Institute on Deafness and Other Communication Disorders (NIDCD)
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT01445405     History of Changes
Other Study ID Numbers: 080071, 08-C-0071
Study First Received: September 30, 2011
Last Updated: October 23, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Proteasome
Bortezomib
NF-kappaB
Cetuximab
Epidermal Growth Factor
Head and Neck Cancer
Squamous Cell Carcinoma
Oral Cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Mouth Neoplasms
Mouth Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Neoplasms, Squamous Cell
Stomatognathic Diseases
Bortezomib
Cetuximab
Cisplatin
Antineoplastic Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014