Phase I/II trial to study the effectiveness of combining BMS-247550 with cisplatin in
treating patients who have metastatic or recurrent head and neck cancer. Drugs used in
chemotherapy use different ways to stop tumor cells from dividing so they stop growing or
die. Combining more than one drug may kill more tumor cells.
I. Determine the recommended phase II dose of BMS-247550 when administered with cisplatin in
patients with metastatic or recurrent squamous cell carcinoma of the head and neck. (Phase
I) II. Determine the toxic effects of this regimen in these patients. III. Determine the
response rate, time to progression, and survival of patients treated with this regimen.
(Phase II) IV. Determine the pharmacokinetics of this regimen in these patients. V.
Correlate selected markers from peripheral blood mononuclear cells and tumor samples with
toxicity and response in patients treated with this regimen.
OUTLINE: This is an open-label, dose-escalation study of BMS-247550.
Phase I: Patients receive BMS-247550 IV over 3 hours and cisplatin IV over 30-60 minutes on
day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable
Cohorts of 3-6 patients receive escalating doses of BMS-247550 until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6
patients experience dose-limiting toxicity. Once the MTD is determined, up to 10 additional
patients receive treatment as above at the recommended phase II dose of BMS-247550.
Phase II: Patients receive treatment as in Phase I at the recommended phase II dose of
- Histologically confirmed squamous cell carcinoma of the head and neck considered
incurable by surgery or radiotherapy
- No nasopharyngeal disease as primary site
- Extensive, local-regional or distant metastatic disease
- Newly diagnosed OR
- Recurrent disease after initial treatment with surgery or radiotherapy
(including neoadjuvant chemotherapy or concurrent chemoradiotherapy)
- Measurable disease
- If only site of measurable disease is in a previously irradiated area, disease
progression after radiotherapy must be documented
- 18 and over
- ECOG 0-1
- Granulocyte count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin no greater than 2.0 mg/dL
- Transaminases no greater than 2 times upper limit of normal (ULN) (5 times ULN if
- Creatinine no greater than 1.5 mg/dL
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No evidence of active infection
- No other malignancy within the past 2 years except curatively treated stage 0 or I
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy for recurrent disease
- At least 6 months since prior radiotherapy and recovered
- Recovered from prior surgery