Aurora Kinase Inhibitor AT9283 in Treating Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma
|ClinicalTrials.gov Identifier: NCT00443976|
Recruitment Status : Completed
First Posted : March 7, 2007
Last Update Posted : November 28, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Non-Hodgkins Lymphoma Unspecified Adult Solid Tumor, Protocol Specific||Drug: Aurora kinase inhibitor AT9283||Phase 1|
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of AT9283 Given As a 24 Hour Infusion on Days 1 and 8 Every Three Weeks in Patients With Advanced Incurable Malignancy|
|Study Start Date :||January 2007|
|Primary Completion Date :||January 2012|
|Study Completion Date :||January 2012|
Drug: Aurora kinase inhibitor AT9283
The starting dose of AT9283 will be 1.5 mg/m2 given as a 24 hour IV infusion on Days 1 and 8 every three weeks.
- Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283) [ Time Frame: 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).
- Recommended phase II dose of AT9283 [ Time Frame: 1 year ]RPTD defined as one dose lower than MTD.
- Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283 [ Time Frame: every 3 weeks ]Adverse events graded using NCI CTCAE V3.0
- Pharmacokinetic profile of AT9283 [ Time Frame: cycle one only ]PK samples collected on all patients during cycle 1 as described in protocol section 17.2.
- Efficacy of AT9283 [ Time Frame: every 6 weeks ]All patients with measurable disease were assessed for response using RECIST criteria as described in protocol section 10.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00443976
|Canada, British Columbia|
|BCCA - Vancouver Cancer Centre|
|Vancouver, British Columbia, Canada, V5Z 4E6|
|Ottawa Health Research Institute - General Division|
|Ottawa, Ontario, Canada, K1H 8L6|
|Study Chair:||Karen A. Gelmon, MD||British Columbia Cancer Agency|
|Study Chair:||Susan F. Dent, MD||Ottawa Regional Cancer Centre|