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

NCT00629226 | Completed Phase 1

• 4 other identifiers: 080071, CDR0000588196NCI-08-C-0071CCR 7205NCI-7893
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicities and other toxicities as assessed by NCI CTCAE v3.0

• Maximum tolerated dose of bortezomib when administered in combination with cetuximab and radiotherapy with and without cisplatin

Secondary Outcomes (4)

• Objective response rate

• Progression-free survival

• Overall survival

• Pre-to-post-treatment changes in biomarkers

Study Arms (2)

Group I

EXPERIMENTAL

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.

Biological: cetuximab; Drug: bortezomib; Radiation: intensity-modulated radiation therapy

Group II

EXPERIMENTAL

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.

Biological: cetuximab; Drug: bortezomib; Drug: cisplatin; Radiation: intensity-modulated radiation therapy

Interventions

cetuximab BIOLOGICAL

Given IV

Group I; Group II

bortezomib DRUG

Given IV

Group I; Group II

cisplatin DRUG

Given IV

Group II

intensity-modulated radiation therapy RADIATION

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

Group I; Group II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Cetuximab; Bortezomib; Cisplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Carter Van Waes, MD, PhD

  National Institute on Deafness and Other Communication Disorders (NIDCD)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 1, 2008
• First Posted: March 5, 2008
• Study Start: October 1, 2007
• Primary Completion: December 1, 2010
• Last Updated: September 30, 2011

Record last verified: 2011-09

Locations

US (2)