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

Head and Neck Cancer Clinical Trial

Official title:

Phase I Study of Bortezomib and Cetuximab Without or With Cisplatin in Combination With Radiation Therapy for Advanced Head and Neck Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00629226
• Other study ID #: 080071, CDR0000588196
• Secondary ID: NCI-08-C-0071CCR
• Status: Completed
• Phase: Phase 1
• First received: March 1, 2008
• Last updated: September 29, 2011
• Start date: October 2007

Study information

• Verified date: September 2011
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. primary completion date: December 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed squamous cell carcinoma of the head and neck, including variants or undifferentiated/poorly differentiated carcinoma

• Previously untreated stage IV disease OR residual disease or regionally recurrent disease after prior surgery and/or chemotherapy

• Must be eligible to receive full-dose radiotherapy and be evaluated and accepted for treatment by a Radiation Oncologist

• 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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Biological:
• cetuximab
Given IV

Drug:
• bortezomib
Given IV
• cisplatin
Given IV

Radiation:
• intensity-modulated radiation therapy
Once daily, 5 days a week, for up to 8 weeks

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland
United States	UPMC Cancer Centers	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicities and other toxicities as assessed by NCI CTCAE v3.0			Yes
Primary	Maximum tolerated dose of bortezomib when administered in combination with cetuximab and radiotherapy with and without cisplatin			Yes
Secondary	Objective response rate			No
Secondary	Progression-free survival			No
Secondary	Overall survival			No
Secondary	Pre-to-post-treatment changes in biomarkers			No