Aurora Kinase Inhibitor AT9283 in Treating Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma
- Conditions
- Non-Hodgkins LymphomaUnspecified Adult Solid Tumor, Protocol Specific
- Interventions
- Drug: Aurora kinase inhibitor AT9283
- Registration Number
- NCT00443976
- Lead Sponsor
- NCIC Clinical Trials Group
- Brief Summary
RATIONALE: Aurora kinase inhibitor AT9283 (AT9283) may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of AT9283 in treating patients with advanced or metastatic solid tumors or non-Hodgkin's lymphoma.
- Detailed Description
OBJECTIVES:
* Determine the maximum tolerated dose and recommended phase II dose of Aurora kinase inhibitor AT9283 (AT9283) in patients with incurable advanced or metastatic solid tumors or non-Hodgkin's lymphoma.
* Determine the safety, tolerability, toxicity profile, dose-limiting toxicity, and pharmacokinetic profile of this drug in these patients.
* Correlate the toxicity profile with the pharmacokinetics of this drug in these patients.
* Assess, preliminarily, evidence of antitumor activity of this drug in these patients.
* Determine the pharmacodynamic activity of this drug in these patients and correlate with biological endpoints.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive Aurora kinase inhibitor AT9283 (AT9283) IV over 24 hours on days 1 and 8 . Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of AT9283 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The dose preceding the MTD is the recommended phase II dose (RPTD). Up to 8 additional patients are treated at the RPTD.
Patients treated at the RPTD undergo skin and tumor tissue biopsy and blood collection at baseline and on days 2 and/or 3. Samples are examined by pharmacokinetic and pharmacodynamic analysis, including immunohistochemistry, immunocytochemistry, western blotting, immunoenzyme techniques, flow cytometry, and reverse transcriptase-polymerase chain reaction, for biological markers.
After completion of study treatment, patients are followed at 4 weeks and then every 3 months until disease progression.
PROJECTED ACCRUAL: Up to 30 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AT9283 Aurora kinase inhibitor AT9283 -
- Primary Outcome Measures
Name Time Method Recommended phase II dose of AT9283 1 year RPTD defined as one dose lower than MTD.
Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283 every 3 weeks Adverse events graded using NCI CTCAE V3.0
Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283) 1 year Doses escalated as described in protocol section 4.3. MTD defined as that dose at which ≥ 2/6 or ≥ 2/3 patients experience DLT (as defined in protocol section 4.4).
Pharmacokinetic profile of AT9283 cycle one only PK samples collected on all patients during cycle 1 as described in protocol section 17.2.
- Secondary Outcome Measures
Name Time Method Efficacy of AT9283 every 6 weeks All patients with measurable disease were assessed for response using RECIST criteria as described in protocol section 10.
Trial Locations
- Locations (2)
Ottawa Health Research Institute - General Division
🇨🇦Ottawa, Ontario, Canada
BCCA - Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada