Bortezomib, Cetuximab, and Radiation Therapy With or Without Cisplatin in Treating Patients With Stage IV Head and Neck Cancer

NCT ID: NCT00629226

Last Updated: 2011-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-10-31

Brief Summary

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Radiation therapy uses high energy x- rays to kill tumor cells. Bortezomib and cetuximab may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with cetuximab, radiation therapy, and cisplatin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with cetuximab and radiation therapy with or without cisplatin in treating patients with stage IV head and neck cancer.

Detailed Description

OBJECTIVES:

Primary

• To evaluate the feasibility and toxicity of bortezomib, cetuximab, and radiotherapy with or without cisplatin in patients with stage IV squamous cell carcinoma of the head and neck.
• To identify the maximum tolerated dose of bortezomib for further clinical phase II development.

Secondary

• To evaluate the objective response rate, progression-free survival, and overall survival of patients treated with these regimens.
• To determine the effects of bortezomib and cetuximab with or without cisplatin on inhibiting activation of the NF-kB, EGFR, MAPK, and STAT3 signal pathways, expression of pro-survival and pro-angiogenesis genes regulated by these pathways, and on proliferation, apoptosis, and angiogenesis.

OUTLINE: This is a multicenter, dose-escalation study of bortezomib. Patients are simultaneously accrued to 1 of 2 treatment groups. Patients are initially accrued to group I until there are a sufficient number of patients to establish the maximum tolerated dose (MTD) of bortezomib. Patients are then accrued to group II.

• Group I: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, 11, 22, 25, 29, 32, 43, 46, 50, and 53. Beginning on day 8 or 9, patients undergo standard intensity-modulated radiotherapy (IMRT) once daily, 5 days a week, for up to 8 weeks.

Once the MTD of bortezomib is determined, at least 6 and up to 10 additional patients are accrued and treated at the MTD.

• Group II: Patients receive cetuximab, bortezomib (beginning at one dose level below the MTD determined in group I), and IMRT as in group I. Patients also receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57.

Once the MTD of bortezomib is determined, 6 additional patients are accrued and treated at the MTD.

Patients undergo blood sample collection periodically for correlative laboratory studies. Samples are analyzed for biomarkers by immunohistochemistry, quantitative reverse transcriptase-polymerase chain reaction, and ELISA.

After completion of study therapy, patients are followed periodically for 2-5 years.

Conditions

Head and Neck Cancer

Keywords

stage IV squamous cell carcinoma of the hypopharynx; stage IV squamous cell carcinoma of the larynx; stage IV squamous cell carcinoma of the lip and oral cavity; stage IV squamous cell carcinoma of the oropharynx; stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity; recurrent squamous cell carcinoma of the hypopharynx; recurrent squamous cell carcinoma of the larynx; recurrent squamous cell carcinoma of the lip and oral cavity; recurrent squamous cell carcinoma of the nasopharynx; recurrent squamous cell carcinoma of the oropharynx; recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity

Study Design

• Primary Study Purpose: TREATMENT

Study Groups

Group I

Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29, 36, 43, and 50. Patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, 11, 22, 25, 29, 32, 43, 46, 50, and 53. Beginning on day 8 or 9, patients undergo standard intensity-modulated radiotherapy (IMRT) once daily, 5 days a week, for up to 8 weeks.

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

Given IV

bortezomib

Intervention Type: DRUG

Given IV

intensity-modulated radiation therapy

Intervention Type: RADIATION

Once daily, 5 days a week, for up to 8 weeks

Group II

Patients receive cetuximab, bortezomib (beginning at one dose level below the MTD determined in group I), and IMRT as in group I. Patients also receive cisplatin IV over 1 hour on days 1, 8, 15, 22, 29, 36, 43, 50, and 57.

Group Type: EXPERIMENTAL

cetuximab

Intervention Type: BIOLOGICAL

Given IV

bortezomib

Intervention Type: DRUG

Given IV

cisplatin

Intervention Type: DRUG

Given IV

intensity-modulated radiation therapy

Intervention Type: RADIATION

Once daily, 5 days a week, for up to 8 weeks

Interventions

cetuximab

Given IV

Intervention Type: BIOLOGICAL

bortezomib

Given IV

Intervention Type: DRUG

cisplatin

Given IV

Intervention Type: DRUG

intensity-modulated radiation therapy

Once daily, 5 days a week, for up to 8 weeks

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• No clinically measurable distant disease OR has asymptomatic small distant lesions outside the radiation field ≤ 3 cm in individual or aggregate diameter for which palliation of local and regional disease is clearly warranted
• No previously untreated nasopharyngeal cancer (any stage)

• Recurrent nasopharyngeal carcinoma allowed
• No known brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status (PS) 0-1 OR Karnofsky PS 70-100%
• ANC ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Total bilirubin normal (indirect bilirubin ≤ 3 mg/dL in patients with Gilbert's syndrome)
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine normal OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Adequate cognitive and neurologic function
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to bortezomib, cetuximab, cisplatin, or other agents used in this study
• No peripheral sensory neuropathy ≥ grade 2
• No concurrent uncontrolled illness including, but not limited to, the following:

• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would preclude study compliance
• HIV-negative

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
• More than 3 months since prior cisplatin
• No prior radiotherapy to the head and neck
• No prior systemic EGFR inhibitors
• No prior bortezomib
• No other concurrent investigational agents
• No other concurrent anticancer therapy
• No concurrent antiretroviral therapy
• No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
• No concurrent amifostine

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Principal Investigators

Carter Van Waes, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Institute on Deafness and Other Communication Disorders (NIDCD)

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, United States

UPMC Cancer Centers

Pittsburgh, Pennsylvania, United States

Countries

United States

Other Identifiers

NCI-08-C-0071

Identifier Type: -

Identifier Source: secondary_id

CCR 7205

Identifier Type: -

Identifier Source: secondary_id

NCI-7893

Identifier Type: -

Identifier Source: secondary_id

080071, CDR0000588196

Identifier Type: -

Identifier Source: org_study_id