A Phase 2 Study of SB-715992 in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
A Phase 2 Study of SB-715992 in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
This phase II trial is studying how well SB-715992 works in treating patients with recurrent or metastatic head and neck cancer. Drugs used in chemotherapy, such as SB-715992, work in different ways to stop tumor cells from dividing so they stop growing or die.
PRIMARY OBJECTIVES:
I. To determine the antitumor activity of SB-715992 in recurrent and/or metastatic squamous cell carcinoma of the head and neck using objective response rates (partial and complete responses).
SECONDARY OBJECTIVES:
I. To determine the duration of objective response, rate and duration of stable disease, progression-free, median and overall survival rates of SB-715992 in recurrent and/or metastatic squamous cell carcinoma of the head and neck.
II. To document the safety and tolerability of SB-715992 in recurrent and/or metastatic squamous cell carcinoma of the head and neck.
III. To characterize the population pharmacokinetic (PK) parameters of SB-715992 including an assessment of significant covariates on SB-715992 PK and an assessment of the potential relationships between the pharmacokinetics of SB-715992 and relevant safety and efficacy endpoints.
OUTLINE: This is an open-label, nonrandomized, multicenter study.
Patients receive SB-715992 IV over 1 hour on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients are followed for survival.
Inclusion Criteria:
Patients must have histologically or cytologically confirmed squamous cell carcinoma of the head and neck that is recurrent or metastatic; with the exception of the nasopharynx, all primary sites (including oral cavity, oropharynx, hypopharynx, and larynx) will be eligible; MedDRA disease terms:
Patients may have had a maximum of one prior chemotherapy regimen for recurrent or metastatic disease; patients may enter this study and receive SB-715992 as their first-line therapy for recurrent and/or metastatic disease; prior platinum-based chemotherapy delivered concurrently with radiotherapy, or prior platinum-based induction chemotherapy, is allowed; there must be at least a 4 week interval between any chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy or surgery and study enrollment; exceptions may be made however, for low dose, non-myelosuppressive radiotherapy - please contact the Principal Investigator (Dr. E. Winquist) PRIOR to registration if questions arise about the interpretation of this criterion; for patients who received local therapy prior to study entry, there must be either progression of measurable disease documented within the treatment field, or must have measurable disease outside the treatment field prior to study entry
Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
Life expectancy of greater than 12 weeks.
ECOG performance status 0,1, or 2
Leukocytes >= 3,000/uL
Absolute neutrophil count >= 1,500/uL
Platelets >= 100,000/uL
Total bilirubin =< 1.5 X institutional upper limit of normal
AST(SGOT)/ALT(SGPT) =< 3.0 X institutional upper limit of normal (=< 5.0 X if liver metastases)
Creatinine =< 1.5 X institutional upper limit of normal
Peripheral neuropathy may be no greater than grade 1
Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of SB-715992 will be determined following review of their use by the TREATING RESPONSIBLE investigator; patients receiving nonprohibited medications or substances known to interact with CYP450 isoenzymes may be eligible but should be monitored carefully; questions about eligibility related to concommitant use of medications should be discussed with the Principal Investigator
HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided there is increased vigilance with respect to monitoring INR. If medically appropriate and treatment available, the investigator may also consider switching these patients to LMW heparin, where an interaction with SB-715992 is not expected
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
Patients with non-squamous cell carcinomas of the head and neck or nasopharyngeal cancer
Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from AEs due to agents administered more than 4 weeks earlier
Patients may not have received any other investigational agents within 28 days of study entry
Patients may not receive other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) while on this study
The following lists of medications/substances are moderate to significant inhibitors/inducers of CYP3A4 that, if administered concomitantly with SB-715992, may alter study drug exposure; the use of these medications/substances within 14 days (>= 6 months for amiodarone) prior to the administration of the first dose of SB-715992 through discontinuation from the study is prohibited
Inhibitors of CYP3A4:
Antibiotics: clarithromycin, erythromycin, troleandomycin
Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200 mg/day), voriconazole
Antidepressants: nefazodone, fluovoxamine
Calcium channel blockers: verapamil, diltiazem
Miscellaneous: amiodarone*, grapefruit juice, bitter orange
Inducers of CYP3A4:
Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
History of allergic reactions attributed to compounds of similar chemical or biologic composition to SB-715992
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Pregnant women are excluded from this study because SB-715992 is a mitotic inhibitor with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SB-715992, breastfeeding should be discontinued if the mother is treated with SB-715992