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


Phase 1
18 Years
N/A
Not Enrolling
Both
Head and Neck Cancer

Thank you

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 CentersPittsburgh, Pennsylvania  15232
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral OfficeBethesda, Maryland  20892-1182