Aurora Kinase Inhibitor AT9283 in Treating Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma - Full Text View

Sponsored by:	National Cancer Institute of Canada
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00443976

Purpose

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	Intervention	Phase
Lymphoma Unspecified Adult Solid Tumor, Protocol Specific	Drug: Aurora kinase inhibitor AT9283	Phase I

MedlinePlus related topics: Cancer Lymphoma

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, 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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283) [ Designated as safety issue: Yes ]
Recommended phase II dose of AT9283 [ Designated as safety issue: Yes ]
Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283 [ Designated as safety issue: Yes ]
Pharmacokinetic profile of AT9283 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Efficacy of AT9283 [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	January 2007
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

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: A total of 30 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed diagnosis of 1 of the following:
- Advanced and/or metastatic solid tumor
- Advanced or metastatic non-Hodgkin's lymphoma refractory to standard therapy
Clinically or radiologically documented disease
- No tumor marker elevation as only evidence of disease
No untreated brain or meningeal metastases
- Treated and stable brain metastases allowed provided they are asymptomatic and do not require steroids

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.25 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min
Bilirubin normal
ALT and AST ≤ 2 times ULN (5 times ULN if liver metastases are present)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use two effective methods of contraception
No untreated or uncontrolled hypertension, cardiovascular conditions, or symptomatic cardiac dysfunction
No active or uncontrolled infections
No serious illness or medical condition that would preclude study treatment

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 2 weeks since prior major surgery and recovered
At least 3 weeks since prior palliative radiotherapy and recovered
- Low-dose, nonmyelosuppressive radiotherapy may be allowed
At least 3 weeks since prior chemotherapy for solid tumors and recovered
- No more than 2 prior cytotoxic chemotherapy regimens for metastatic disease
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00443976

Locations

Canada, British Columbia
British Columbia Cancer Agency - Vancouver Cancer Centre	Recruiting
Vancouver, British Columbia, Canada, V5Z 4E6
Contact: Karen Gelmon 604-877-6000
Canada, Ontario
Ottawa Hospital Regional Cancer Centre - General Campus	Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Susan Dent 613-737-7700

Sponsors and Collaborators

National Cancer Institute of Canada

Investigators

Study Chair:	Karen A. Gelmon, MD	British Columbia Cancer Agency
Investigator:	Susan F. Dent, MD	Ottawa Hospital Regional Cancer Centre - General Campus

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000523837, CAN-NCIC-IND181, CAN-NCIC-IND181, ASTEX-CAN-NCIC-IND181
Study First Received:	March 5, 2007
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00443976
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific
recurrent adult Burkitt lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 2 follicular lymphoma
stage III grade 2 follicular lymphoma
stage IV grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 3 follicular lymphoma
recurrent mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma

stage IV adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage IV adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
stage III grade 1 follicular lymphoma

Study placed in the following topic categories:

Lymphoma, Mantle-Cell
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Lymphoma, B-Cell, Marginal Zone
Lymphoma, large-cell, immunoblastic
Lymphoma, B-Cell
Lymphoma, large-cell
Lymphomatoid granulomatosis
Burkitt's lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Waldenstrom macroglobulinemia
Lymphoma
Chronic lymphocytic leukemia

Lymphomatoid Granulomatosis
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Leukemia, B-cell, chronic
Lymphoblastic lymphoma
Mantle cell lymphoma
Recurrence
Lymphatic Diseases
Waldenstrom Macroglobulinemia
Burkitt Lymphoma
B-cell lymphomas
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Follicular lymphoma

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immune System Diseases

ClinicalTrials.gov processed this record on January 16, 2009