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

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00095628
Enrollment
21
Registered
2004-11-08
Start date
2005-01-31
Completion date
2010-07-31
Last updated
2017-03-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma, 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, 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, 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

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.

Interventions

Given IV

OTHERlaboratory biomarker analysis

Correlative studies

OTHERpharmacological study

Correlative studies

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Antitumor Activity of SB-715992 Using Objective Response Rates (Partial and Complete Responses)Up to 18 monthsPer 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

MeasureTime frameDescription
Duration of Objective ResponseUp to 18 monthsPer 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 DiseaseUp to 18 monthsPer 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.
Median Overall Survival of SB-715992Up to 18 monthsOverall 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 ProgressionUp to 18 monthsTime 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.

Other

MeasureTime frameDescription
1 Year Overall Survival12 monthsOverall survival is defined as the time from enrolment until death due to any cause. The Kaplan-Meier method was used to estimate overall survival.

Countries

Canada

Participant flow

Participants by arm

ArmCount
Treatment (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. ispinesib: Given IV laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies
20
Total20

Withdrawals & dropouts

PeriodReasonFG000
Overall StudyDisease progression prior to treatment1

Baseline characteristics

CharacteristicTreatment (Ispinesib)
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
7 Participants
Age, Categorical
Between 18 and 65 years
13 Participants
Age, Continuous60 participants
Gender
Female
3 Participants
Gender
Male
17 Participants
Region of Enrollment
Canada
18 participants
Region of Enrollment
United States
2 participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
— / —
other
Total, other adverse events
20 / 20
serious
Total, serious adverse events
6 / 20

Outcome results

Primary

Antitumor Activity of SB-715992 Using Objective Response Rates (Partial and Complete Responses)

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

Time frame: Up to 18 months

Population: 20 eligible patients were analyzed

ArmMeasureValue (NUMBER)
Treatment (Ispinesib)Antitumor Activity of SB-715992 Using Objective Response Rates (Partial and Complete Responses)0 participants
Secondary

Duration of Objective Response

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

Time frame: Up to 18 months

Population: Data were not collected because 0 participants showed a response.

Secondary

Median Overall Survival of SB-715992

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.

Time frame: Up to 18 months

ArmMeasureValue (MEDIAN)
Treatment (Ispinesib)Median Overall Survival of SB-7159923.5 months
Secondary

Median Time to Progression

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.

Time frame: Up to 18 months

ArmMeasureValue (MEDIAN)
Treatment (Ispinesib)Median Time to Progression1.4 months
Secondary

Number of Participants With Clinical and Objective Stable Disease

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.

Time frame: Up to 18 months

ArmMeasureValue (NUMBER)
Treatment (Ispinesib)Number of Participants With Clinical and Objective Stable Disease5 participants
Other Pre-specified

1 Year Overall Survival

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.

Time frame: 12 months

ArmMeasureValue (NUMBER)
Treatment (Ispinesib)1 Year Overall Survival20 percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026