Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Bortezomib and Radiation Therapy in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active Over 18 NCI NCI-01-C-0104J NCT00016003, 751

Special Category: NIH Clinical Center trial, NCI Web site featured trial

Objectives

1. Determine the maximum tolerated dose of bortezomib with concurrent radiotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Entry Criteria

Disease Characteristics:

• Histologically confirmed squamous cell carcinoma of the head and neck
  • Local-regional disease that is amenable to radiotherapy
  • Persistent, recurrent, or unresectable regional disease with OR without metastatic disease after standard curative therapy



• No known brain metastases

Prior/Concurrent Therapy:

Biologic therapy:

• At least 4 weeks since prior immunotherapy
• No concurrent biologic therapy for treatment of malignancy
• No concurrent colony-stimulating factors during first course of study therapy

Chemotherapy:

• At least 4 weeks since prior chemotherapy
• No other concurrent chemotherapy for treatment of malignancy

Endocrine therapy:

• No concurrent endocrine therapy for treatment of malignancy

Radiotherapy:

• More than 6 months since prior radiotherapy to the head and neck
  • At least 1 month since prior palliative radiotherapy to any other sites and recovered

Surgery:

• At least 4 weeks since prior surgery

Other:

• No other concurrent investigational agent or therapy for treatment of malignancy
• No concurrent amifostine

Patient Characteristics:

Age:

• Over 18

Performance status:

• ECOG 0-2

  OR

• Karnofsky 50-100%

Life expectancy:

• More than 3 months

Hematopoietic:

• Absolute neutrophil count greater than 1,500/mm³
• Platelet count greater than 100,000/mm³

Hepatic:

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT/SGPT less than 2.5 times ULN

Renal:

• Creatinine less than 1.5 times ULN

  OR

• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• No symptomatic congestive heart failure
• No myocardial infarction within the past 6 months
• No unstable angina pectoris
• No unstable cardiac arrhythmia requiring assessment for clinical intervention
• No postural hypotension due to severe baroreceptor dysfunction after prior radiotherapy and/or surgery that is not amenable to volume repletion, defined as 1 of the following:
  • Systolic blood pressure remains at 100 mm Hg or less with absence of orthostatic changes or symptoms
  • Systolic blood pressure remains at 120 mm Hg or less with orthostatic changes and absence of symptoms
• No uncorrectable hyponatremia of 130 mEq/L or greater

Other:

• No known HIV positivity
• No other prior malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
• No concurrent uncontrolled illness
• No active infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception

Expected Enrollment

A maximum of 51 patients (30 with prior radiotherapy and 21 with no prior radiotherapy) will be accrued for this study within 12 months.

Outcomes

Toxicity and maximum tolerated dose (MTD) as assessed by CTC version 2.0 during treatment and weekly for 3 months after treatment

Response rate as assessed by RECIST criteria at end of treatment and 3 months after treatment

Outline

This is a dose-escalation study. Patients are stratified according to prior radiotherapy (yes vs no).

Patients receive bortezomib IV over 3-5 seconds twice weekly. Patients also receive radiotherapy on days 1-5 (days 2-5 only for the first course). Courses repeat every week for 3 weeks. Patients then receive radiotherapy alone on days 1-5 of weeks 4 and 5. Treatment with bortezomib and radiotherapy resumes in weeks 6 and 7 (for patients with prior radiotherapy) or weeks 6, 7, and 8 (for patients with no prior radiotherapy) in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at weeks 1-8, at week 12, and then monthly for 1 year.

Lebowitz PF, Harkins C, Conley B, et al.: Concomitant therapy with proteasome inhibitor, bortezomib, and radiation in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) . [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2010, 499, 2003.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Carter Van Waes, MD, PhD, Protocol chair		Ph: 301-402-4216

U.S.A.
Maryland
	Bethesda
	NCI - Center for Cancer Research
		Clinical Trials Office - NCI - Center for Cancer Research	Ph:  888-624-1937
	NIH - Warren Grant Magnuson Clinical Center
		Clinical Trials Office - Warren Grant Magnusen Clinical Center - NCI Clinical Trials Referral Office	Ph:  888-NCI-1937

Related Information

Featured trial article

Registry Information
Official Title		A Phase I Study of Concomitant Therapy with Proteasome Inhibitor PS-341 and Radiation in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
Trial Start Date		2001-03-01
Trial Completion Date		2008-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00016003
Date Submitted to PDQ		2001-03-02
Information Last Verified		2008-11-30

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