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| ID | Type | Description | Link |
|---|---|---|---|
| CDR0000523837 | Registry Identifier | PDQ | |
| CAN-NCIC-IND181 | Registry Identifier | NCI US - Physician Data Query | |
| ASTEX-CAN-NCIC-IND181 | Registry Identifier | Astex Therapeutics Inc. |
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| Name | Class |
|---|---|
| Astex Pharmaceuticals, Inc. | INDUSTRY |
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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.
OBJECTIVES:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AT9283 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aurora kinase inhibitor AT9283 | Drug | 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283) | 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). | 1 year |
| Recommended phase II dose of AT9283 | RPTD defined as one dose lower than MTD. | 1 year |
| Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283 | Adverse events graded using NCI CTCAE V3.0 | every 3 weeks |
| Pharmacokinetic profile of AT9283 | PK samples collected on all patients during cycle 1 as described in protocol section 17.2. | cycle one only |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of AT9283 | All patients with measurable disease were assessed for response using RECIST criteria as described in protocol section 10. | every 6 weeks |
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DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed diagnosis of 1 of the following:
Clinically or radiologically documented disease
No untreated brain or meningeal metastases
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
At least 2 weeks since prior major surgery and recovered
At least 3 weeks since prior palliative radiotherapy and recovered
At least 3 weeks since prior chemotherapy for solid tumors and recovered
At least 4 weeks since prior steroids
No limitations on prior therapy for patients with non-Hodgkin's lymphoma
Prior hormonal, immunologic, biologic or signal transduction inhibitor therapy allowed
No other concurrent investigational agents
No other concurrent anticancer therapy
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| Name | Affiliation | Role |
|---|---|---|
| Karen A. Gelmon, MD | British Columbia Cancer Agency | Study Chair |
| Susan F. Dent, MD | Ottawa Regional Cancer Centre | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| BCCA - Vancouver Cancer Centre | Vancouver | British Columbia | V5Z 4E6 | Canada | ||
| Ottawa Health Research Institute - General Division |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24072436 | Result | Dent SF, Gelmon KA, Chi KN, Jonker DJ, Wainman N, Capier CA, Chen EX, Lyons JF, Seymour L. NCIC CTG IND.181: phase I study of AT9283 given as a weekly 24 hour infusion in advanced malignancies. Invest New Drugs. 2013 Dec;31(6):1522-9. doi: 10.1007/s10637-013-0018-9. Epub 2013 Sep 27. |
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| Ottawa |
| Ontario |
| K1H 8L6 |
| Canada |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D002051 | Burkitt Lymphoma |
| D008224 | Lymphoma, Follicular |
| D020522 | Lymphoma, Mantle-Cell |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D016400 | Lymphoma, Large-Cell, Immunoblastic |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D018442 | Lymphoma, B-Cell, Marginal Zone |
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D008258 | Waldenstrom Macroglobulinemia |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D016393 | Lymphoma, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D006402 | Hematologic Diseases |
| D015448 | Leukemia, B-Cell |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D054219 | Neoplasms, Plasma Cell |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006474 | Hemorrhagic Disorders |
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