Phase I Study of Bortezomib and Cetuximab Without or With Cisplatin in Combination With Radiation Therapy for Advanced Head and Neck Cancer
18 Years
N/A
Both
Head and Neck Cancer
Trial Information
Phase I Study of Bortezomib and Cetuximab Without or With Cisplatin in Combination With Radiation Therapy for Advanced Head and Neck Cancer
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Dose-limiting toxicities and other toxicities as assessed by NCI CTCAE v3.0
Safety Issue:
Yes
Principal Investigator
Carter Van Waes, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Institute on Deafness and Other Communication Disorders (NIDCD)
Authority:
United States: Food and Drug Administration
Study ID:
080071, CDR0000588196
NCT ID:
NCT00629226
Start Date:
October 2007
Completion Date:
Related Keywords:
- Head and Neck Cancer
- 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
- Head and Neck Neoplasms
Name | Location |
|---|---|
| UPMC Cancer Centers | Pittsburgh, Pennsylvania 15232 |
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda, Maryland 20892-1182 |
