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

Primary Purpose

Head and Neck Cancer

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

cetuximab

bortezomib

cisplatin

intensity-modulated radiation therapy

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
UPMC Cancer Centers

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Group I

Group II

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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 Outcome Measures

Objective response rate

Progression-free survival

Overall survival

Pre-to-post-treatment changes in biomarkers

Full Information

NCT ID

NCT00629226

First Posted

March 1, 2008

Last Updated

September 29, 2011

Sponsor

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00629226

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2011

Overall Recruitment Status

Completed

Study Start Date

October 2007 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor

National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Enrollment

46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Group I

Arm Type

Experimental

Arm Description

Arm Title

Group II

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

cetuximab

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

bortezomib

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

cisplatin

Intervention Description

Given IV

Intervention Type

Radiation

Intervention Name(s)

intensity-modulated radiation therapy

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Title

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

Secondary Outcome Measure Information:

Title

Objective response rate

Title

Progression-free survival

Title

Overall survival

Title

Pre-to-post-treatment changes in biomarkers

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carter Van Waes, MD, PhD

Organizational Affiliation

National Institute on Deafness and Other Communication Disorders (NIDCD)

Official's Role

Principal Investigator

Facility Information:

Facility Name

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20892-1182

Country

United States

Facility Name

UPMC Cancer Centers

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15232

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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