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A Randomized Phase II Non-Comparative Study of SB-715992 Given Weekly or Every Three Weeks in Advanced or Metastatic Colorectal Cancer


Phase 2
18 Years
N/A
Not Enrolling
Both
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

Thank you

Trial Information

A Randomized Phase II Non-Comparative Study of SB-715992 Given Weekly or Every Three Weeks in Advanced or Metastatic Colorectal Cancer


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.


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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective response (CR or PR) as determined by the RECIST criteria

Outcome Time Frame:

Up to 5 years

Safety Issue:

No

Principal Investigator

Syma Iqbal

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02834

NCT ID:

NCT00103311

Start Date:

January 2005

Completion Date:

Related Keywords:

  • 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
  • Colonic Neoplasms
  • Rectal Neoplasms
  • Colorectal Neoplasms

Name

Location

City of HopeDuarte, California  91010