Aurora Kinase Inhibitor AT9283 in Treating Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma
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|ClinicalTrials.gov Identifier: NCT00443976|
Recruitment Status : Completed
First Posted : March 7, 2007
Last Update Posted : April 8, 2020
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|
|Actual Study Start Date :||January 4, 2007|
|Actual Primary Completion Date :||April 9, 2010|
|Actual Study Completion Date :||January 6, 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|