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
18 Years
N/A
Both
Non-Hodgkins Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
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
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.
Inclusion 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:
- 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283)
Outcome Description:
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).
Outcome Time Frame:
1 year
Safety Issue:
Yes
Principal Investigator
Karen A. Gelmon, MD
Investigator Role:
Study Chair
Investigator Affiliation:
British Columbia Cancer Agency
Authority:
Canada: Health Canada
Study ID:
I181
NCT ID:
NCT00443976
Start Date:
January 2007
Completion Date:
January 2012
Related Keywords:
- Non-Hodgkins Lymphoma
- Unspecified Adult Solid Tumor, Protocol Specific
- 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
- stage IV grade 1 follicular lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- recurrent marginal zone lymphoma
- stage III marginal zone lymphoma
- stage IV marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage IV small lymphocytic lymphoma
- recurrent adult grade III lymphomatoid granulomatosis
- adult grade III lymphomatoid granulomatosis
- Waldenstrom macroglobulinemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Lymphoma, Large-Cell, Immunoblastic
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