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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00103311
First received: February 7, 2005
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: ispinesib
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Non-Comparative Study of SB-715992 Given Weekly or Every Three Weeks in Advanced or Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response (CR or PR) as determined by the RECIST criteria [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Will be estimated using the product-limit method of Kaplan and Meier by arm.

  • Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Will be estimated using the product-limit method of Kaplan and Meier by arm. Greenwood standard errors will be calculated for each arm.

  • Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Greenwood standard errors will be calculated for each arm.


Enrollment: 76
Study Start Date: January 2005
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Given IV
Other: laboratory biomarker analysis
Correlative studies
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
Given IV
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103311

Locations
United States, California
City of Hope
Duarte, California, United States, 91010
Sponsors and Collaborators
Investigators
Principal Investigator: Syma Iqbal Beckman Research Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00103311     History of Changes
Other Study ID Numbers: NCI-2012-02834, NCI-2012-02834, PHII-51, 6800
Study First Received: February 7, 2005
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on August 20, 2014