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

Stage IV Squamous Cell Carcinoma of the Hypopharynx Clinical Trial

Official title:

A Phase 2 Study of SB-715992 in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00095628
• Other study ID #: NCI-2012-03091
• Secondary ID: PHL-0316803N01CM
• Status: Completed
• Phase: Phase 2
• First received: November 5, 2004
• Last updated: May 7, 2013
• Start date: January 2005

Study information

• Verified date: May 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 33
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Laryngeal Diseases
• Laryngeal Neoplasms
• Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma
• Oropharyngeal Neoplasms
• Paranasal Sinus Neoplasms
• Recurrent Metastatic Squamous Neck Cancer With Occult Primary
• Recurrent Salivary Gland Cancer
• Recurrent Squamous Cell Carcinoma of the Hypopharynx
• Recurrent Squamous Cell Carcinoma of the Larynx
• Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity
• Recurrent Squamous Cell Carcinoma of the Oropharynx
• Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Recurrent Verrucous Carcinoma of the Larynx
• Recurrent Verrucous Carcinoma of the Oral Cavity
• Salivary Gland Neoplasms
• Stage IV Squamous Cell Carcinoma of the Hypopharynx
• Stage IV Squamous Cell Carcinoma of the Larynx
• 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
• Stage IVA Salivary Gland Cancer
• Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Stage IVB Salivary Gland Cancer
• Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity
• Stage IVC Salivary Gland Cancer
• Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

Intervention

Drug:
• ispinesib
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital Phase 2 Consortium	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Antitumor activity of SB-715992 using objective response rates (partial and complete responses)	Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon ranksum tests may be substituted if necessary. 95% confidence intervals will be constructed and selected results will be illustrated using figures and plots.	Up to 18 months	No
Secondary	Duration of objective response	Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon ranksum tests may be substituted if necessary. 95% confidence intervals will be constructed and selected results will be illustrated using figures and plots.	Up to 18 months	No
Secondary	Rate and duration of stable disease	Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon ranksum tests may be substituted if necessary. 95% confidence intervals will be constructed and selected results will be illustrated using figures and plots.	Up to 18 months	No
Secondary	Median and overall survival rates of SB-715992	Summary statistics, such as the mean, median, counts and proportion, will be used to summarize the patients. Survival estimates will be computed using the Kaplan-Meier method. Potential association between variables will be measured using Pearson correlation coefficients, chi-square tests, one- or two-sample t-tests or logistic regression analyses as appropriate. Non-parametric tests such as Spearman correlation coefficients, Fisher's exact tests and Wilcoxon ranksum tests may be substituted if necessary. 95% confidence intervals will be constructed and selected results will be illustrated.	Up to 18 months	No