Bortezomib and Radiation Therapy in Treating Patients With Recurrent or Metastatic Head and Neck Cancer
|Phase I||Treatment||Completed||Over 18||NCI||NCI-01-C-0104|
Special Category: NCI Web site featured trial
- Determine the maximum tolerated dose of bortezomib with concurrent radiotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
- 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
- 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
- At least 4 weeks since prior chemotherapy and recovered
- No other concurrent chemotherapy for treatment of malignancy
- No concurrent endocrine therapy for treatment of malignancy
- 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
- At least 4 weeks since prior surgery
- No other concurrent investigational agent or therapy for treatment of malignancy
- No concurrent amifostine
- Over 18
- More than 3 months
- Absolute neutrophil count greater than 1,500/mm3
- Platelet count greater than 100,000/mm3
- Bilirubin less than 1.5 times upper limit of normal (ULN)
- SGOT/SGPT less than 2.5 times ULN
- 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
- 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
A maximum of 51 patients (30 with prior radiotherapy and 21 with no prior radiotherapy) will be accrued for this study within 12 months.
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
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.Published Results
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 Lead Organizations
NCI - Center for Cancer Research
|Carter Van Waes, MD, PhD, Protocol chair|
|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||2012-12-12|
|Registered in ClinicalTrials.gov||NCT00016003|
|Date Submitted to PDQ||2001-03-02|
|Information Last Verified||2009-06-14|
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.