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CompletedNCT00103311Updated Mar 2, 2015Results posted

SB-715992 in Treating Patients With Advanced or Metastatic Colorectal Cancer

A Phase 2 interventional study of ispinesib and laboratory biomarker analysis in Recurrent Colon Cancer, Recurrent Rectal Cancer and Stage IIIA Colon Cancer, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-03-02.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
64
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This randomized phase II trial is studying how well SB-715992 works in treating patients with advanced or metastatic colorectal cancer. Drugs used in chemotherapy, such as SB-715992, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine the objective response rate in patients with advanced or metastatic colorectal cancer treated with SB-715992 once a week for 3 weeks, every 28 days and SB-715992 once every 21 days.

SECONDARY OBJECTIVES:

I. To determine the time to tumor progression, progression free and overall survival of patients and toxicity in patients with advanced or metastatic colorectal cancer treated with SB-715992 once a week for 3 weeks, every 28 days and SB-715992 once every 21 days.

II. 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.

IV. To examine cytoskeletal morphology changes in response to SB-715992 in peripheral blood mononuclear cells and tumors by fluorescent immunohistochemistry.

V. To evaluate mRNA expression of betaΙΙΙ-tubulin and KSP in archival tumor tissue.

VI. To determine the frequency of genomic polymorphisms in genes targeted by SB-715992 (measured in peripheral blood mononuclear cells) and to assess whether germline polymorphisms (DNA) of genes targeted by SB-715992 (KSP inhibitor) are associated with toxicity and clinical outcome in patients with colorectal cancer. Further, whether genes involved with the metabolism (CYP3A4) and resistance (MDR1) affect the outcome in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive SB-715992 IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: 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.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

02

Conditions studied

  • Recurrent Colon Cancer
  • Recurrent Rectal Cancer
  • Stage IIIA Colon Cancer
  • Stage IIIA Rectal Cancer
  • Stage IIIB Colon Cancer
  • Stage IIIB Rectal Cancer
  • Stage IIIC Colon Cancer
  • Stage IIIC Rectal Cancer
  • Stage IVA Colon Cancer
  • Stage IVA Rectal Cancer
  • Stage IVB Colon Cancer
  • Stage IVB Rectal Cancer
03

In context

Colonic Neoplasms

1,485 studies on the registry are indexed under Colonic Neoplasms; 362 are open to participants now.

This study's enrollment of 64 is below the median of 89 across 1,067 interventional studies indexed under Colonic Neoplasms.

Browse Colonic Neoplasms studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,554 studies on the registry; 334 are open to participants now.

Of its 407 completed or terminated interventional studies of FDA-regulated products, 370 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patients must have histologically or cytologically confirmed advanced/metastatic colorectal cancer
  • 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
  • Patients must have received prior therapy (in any setting) with 5-FU, CPT-11, and oxaliplatin; patients may have received prior erbitux and bevacizumab, but it is not required
  • Patients must have received at least one prior chemotherapy regimen for advanced disease
  • Tumor must be accessible for biopsy or paraffin embedded tissue must be available for review of their biopsy specimen
  • Life expectancy of > 12 weeks
  • ECOG performance status 0-2 (Karnofsky >= 50%)
  • Leukocytes >= 3,000/μL
  • Absolute neutrophil count >= 1,500/μL
  • Platelets >= 100,000/μL
  • Hemoglobin >= 9 mg/dL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal
  • Creatinine =\< 1.5 X institutional upper limit of normal OR creatinine clearance >= 60 mL/min/1.73 m\^2
  • 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

Exclusion Criteria:

  • 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
  • Prohibited medications; SB-715992 is a moderate to significant in vitro inhibitor of CYP3A4; 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; breastfeeding should be discontinued if the mother is treated with SB-715992
  • HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
64 participants (actual)

Study arms

  • Experimental
    Arm I

    Patients receive SB-715992 IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: ispinesib · Other: laboratory biomarker analysis

  • Experimental
    Arm II

    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.

    Drug: ispinesib · Other: laboratory biomarker analysis

Interventions

  • Given IV

  • Otherlaboratory biomarker analysis

    Correlative studies

06

What researchers measure

Primary outcomes

  1. Objective Response (CR or PR) as Determined by the RECIST Criteria

    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 lesions; Overall Response (OR) = CR + PR

    Time frame: Up to 5 years

Secondary outcomes

  1. Progression-free Survival

    Will be estimated using the product-limit method of Kaplan and Meier by arm. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

    Time frame: From the date of registration to the date of documented PSA progression, assessed up to 6 months

  2. Overall Survival

    Will be estimated using the product-limit method of Kaplan and Meier by arm.

    Time frame: From the date of registration to the date of death, assessed up to 12 months

07

Results

Posted Mar 2, 2015

Participant flow

Participant flow — Overall Study
MilestoneArm IArm II
Started3331
Completed2930
Not completed41
Withdrew: Lost to follow-up10
Withdrew: Withdrawal by subject21
Withdrew: Adverse event10

Outcome measures

PrimaryObjective Response (CR or PR) as Determined by the RECIST Criteria

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 lesions; Overall Response (OR) = CR + PR

Time frame:
Up to 5 years
Reported as:
Number · participants
Objective Response (CR or PR) as Determined by the RECIST Criteria
participantsArm IArm II
Objective Response (CR or PR) as Determined by the RECIST Criteria00
SecondaryProgression-free Survival

Will be estimated using the product-limit method of Kaplan and Meier by arm. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time frame:
From the date of registration to the date of documented PSA progression, assessed up to 6 months
Reported as:
Median · weeks
Progression-free Survival
weeksArm IArm II
Progression-free Survival7.0 (6.3 to 7.3)5.3 (5.0 to 5.9)
SecondaryOverall Survival

Will be estimated using the product-limit method of Kaplan and Meier by arm.

Time frame:
From the date of registration to the date of death, assessed up to 12 months
Reported as:
Median · months
Overall Survival
monthsArm IArm II
Overall Survival3.6 (2.5 to 8.2)4.5 (3.7 to 7.0)

Adverse events

Collected over Adverse events were over a period of 4 years.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Arm I—14/33 (42.4%)33/33 (100%)
Arm II—13/31 (41.9%)31/31 (100%)
Most frequent serious events
Showing 10 of 35
Most frequent serious events
EventArm IArm II
Neutrophil count decreasedInvestigations0/338/31
Disease progressionGeneral disorders2/334/31
NauseaGastrointestinal disorders4/331/31
DehydrationMetabolism and nutrition disorders4/331/31
HyperbilirubinemiaInvestigations1/333/31
Abdominal painGastrointestinal disorders3/331/31
VomitingGastrointestinal disorders3/331/31
Gallbladder obstructionHepatobiliary disorders0/332/31
Alanine aminotransferase increasedInvestigations0/332/31
Alkaline phosphatase increasedInvestigations1/332/31
Most frequent other events
Showing 10 of 99
Most frequent other events
EventArm IArm II
Disease progressionGeneral disorders29/3324/31
FatigueGeneral disorders20/3319/31
Hemoglobin decreasedBlood and lymphatic system disorders17/3318/31
Alkaline phosphatase increasedInvestigations13/3316/31
Neutrophil count decreasedInvestigations9/3315/31
Abdominal painGastrointestinal disorders14/3310/31
Aspartate aminotransferase increasedInvestigations13/3313/31
LeukopeniaInvestigations6/3313/31
AnorexiaMetabolism and nutrition disorders13/3311/31
HyperglycemiaMetabolism and nutrition disorders11/3310/31

Baseline characteristics

Age, Continuous
Age, Continuous(years)Arm IArm IITotal
Median59 (28 to 82)60 (35 to 80)59 (28 to 82)
Sex: Female, Male
Sex: Female, Male(Participants)Arm IArm IITotal
Female141327
Male191837
Region of Enrollment
Region of Enrollment(participants)Arm IArm IITotal
United States333164
08

Study locations

1 site
  • University of Southern California, Norris
    Los Angeles, California 90033, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 2, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00103311
Responsible party
Sponsor
First posted
Feb 8, 2005
Start date
Jan 2005
Primary completion
Jan 2010
Completion
Sep 2010
Results posted
Mar 2, 2015
Last update
Mar 2, 2015

Study contacts

Syma Iqbal, MD
principal investigator · University of Southern California, Norris
View the source record on ClinicalTrials.gov ↗

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