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
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.
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.
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 →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.
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.
Exclusion Criteria:
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:
Miscellaneous: amiodarone*, grapefruit juice, bitter orange
Inducers of CYP3A4:
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
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
Given IV
Correlative studies
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
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
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
| Milestone | Arm I | Arm II |
|---|---|---|
| Started | 33 | 31 |
| Completed | 29 | 30 |
| Not completed | 4 | 1 |
| Withdrew: Lost to follow-up | 1 | 0 |
| Withdrew: Withdrawal by subject | 2 | 1 |
| Withdrew: Adverse event | 1 | 0 |
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
| participants | Arm I | Arm II |
|---|---|---|
| Objective Response (CR or PR) as Determined by the RECIST Criteria | 0 | 0 |
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.
| weeks | Arm I | Arm II |
|---|---|---|
| Progression-free Survival | 7.0 (6.3 to 7.3) | 5.3 (5.0 to 5.9) |
Will be estimated using the product-limit method of Kaplan and Meier by arm.
| months | Arm I | Arm II |
|---|---|---|
| Overall Survival | 3.6 (2.5 to 8.2) | 4.5 (3.7 to 7.0) |
Collected over Adverse events were over a period of 4 years.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Arm I | — | 14/33 (42.4%) | 33/33 (100%) |
| Arm II | — | 13/31 (41.9%) | 31/31 (100%) |
| Event | Arm I | Arm II |
|---|---|---|
| Neutrophil count decreasedInvestigations | 0/33 | 8/31 |
| Disease progressionGeneral disorders | 2/33 | 4/31 |
| NauseaGastrointestinal disorders | 4/33 | 1/31 |
| DehydrationMetabolism and nutrition disorders | 4/33 | 1/31 |
| HyperbilirubinemiaInvestigations | 1/33 | 3/31 |
| Abdominal painGastrointestinal disorders | 3/33 | 1/31 |
| VomitingGastrointestinal disorders | 3/33 | 1/31 |
| Gallbladder obstructionHepatobiliary disorders | 0/33 | 2/31 |
| Alanine aminotransferase increasedInvestigations | 0/33 | 2/31 |
| Alkaline phosphatase increasedInvestigations | 1/33 | 2/31 |
| Event | Arm I | Arm II |
|---|---|---|
| Disease progressionGeneral disorders | 29/33 | 24/31 |
| FatigueGeneral disorders | 20/33 | 19/31 |
| Hemoglobin decreasedBlood and lymphatic system disorders | 17/33 | 18/31 |
| Alkaline phosphatase increasedInvestigations | 13/33 | 16/31 |
| Neutrophil count decreasedInvestigations | 9/33 | 15/31 |
| Abdominal painGastrointestinal disorders | 14/33 | 10/31 |
| Aspartate aminotransferase increasedInvestigations | 13/33 | 13/31 |
| LeukopeniaInvestigations | 6/33 | 13/31 |
| AnorexiaMetabolism and nutrition disorders | 13/33 | 11/31 |
| HyperglycemiaMetabolism and nutrition disorders | 11/33 | 10/31 |
| Age, Continuous(years) | Arm I | Arm II | Total |
|---|---|---|---|
| Median | 59 (28 to 82) | 60 (35 to 80) | 59 (28 to 82) |
| Sex: Female, Male(Participants) | Arm I | Arm II | Total |
|---|---|---|---|
| Female | 14 | 13 | 27 |
| Male | 19 | 18 | 37 |
| Region of Enrollment(participants) | Arm I | Arm II | Total |
|---|---|---|---|
| United States | 33 | 31 | 64 |
This study is completed, as verified in Oct 2013. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Ispinesib
National Cancer Institute (NCI) →