SB-715992 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Phase 2

Completed

Conditions: Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity
Stage IV Squamous Cell Carcinoma of the Oropharynx
Stage IV Verrucous Carcinoma of the Larynx
Stage IV Verrucous Carcinoma of the Oral Cavity
Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
Recurrent Metastatic Squamous Neck Cancer With Occult Primary
Recurrent Squamous Cell Carcinoma of the Hypopharynx
Recurrent Salivary Gland Cancer
Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
Recurrent Squamous Cell Carcinoma of the Larynx

Interventions: Drug: ispinesib
Other: laboratory biomarker analysis
Other: pharmacological study

Registration Number: NCT00095628

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 21

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:
- Oral neoplasms NOS, 10031008
- Oropharyngeal cancer recurrent, 10031098
- Hypopharyngeal cancer recurrent, 10021044
- Laryngeal cancer recurrent, 10023828
- Maxillofacial sinus neoplasm, 10026956
- Head and neck, 90002024
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
    - Use of amiodarone within 6 months prior to the administration of the first dose of SB-715992 is prohibited
- Inducers of CYP3A4:
  - Anticonvulsants: phenytoin, carbamazepine, Phenobarbital, oxcarbazepine
  - Antibiotics: rifampin, rifabutin, rifapentine
  - Miscellaneous: St. John's wort, modafinil
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (ispinesib)	laboratory biomarker analysis	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.
Treatment (ispinesib)	pharmacological 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.
Treatment (ispinesib)	ispinesib	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.

Primary Outcome Measures

Name	Time	Method
Antitumor Activity of SB-715992 Using Objective Response Rates (Partial and Complete Responses)	Up to 18 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesion

Secondary Outcome Measures

Name	Time	Method
Median Overall Survival of SB-715992	Up to 18 months	Overall survival is defined as the time from enrolment until death due to any cause. The Kaplan-Meier method was used to estimate overall survival.
Median Time to Progression	Up to 18 months	Time to progression (TTP) is defined as the time from enrolment onto the study until progression or death. The Kaplan-Meier method was used to estimate TTP.
Duration of Objective Response	Up to 18 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesion
Number of Participants With Clinical and Objective Stable Disease	Up to 18 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease.