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

NCIC Clinical Trials Group

Status and phase

Completed

Phase 1

Conditions

Non-Hodgkins Lymphoma

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: Aurora kinase inhibitor AT9283

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT00443976

CDR0000523837 (Registry Identifier)

ASTEX-CAN-NCIC-IND181 (Registry Identifier)

CAN-NCIC-IND181 (Registry Identifier)

I181

Details and patient eligibility

About

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.

Full 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: Up to 30 patients will be accrued for this study.

Enrollment

35 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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