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

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00443976
• Other study ID #: I181
• Secondary ID: CDR0000523837CAN
• Status: Completed
• Phase: Phase 1
• Start date: January 30, 2007
• Est. completion date: January 6, 2012

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: January 6, 2012
• Est. primary completion date: April 9, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkins Lymphoma
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

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.

Locations

Country	Name	City	State
Canada	Ottawa Health Research Institute - General Division	Ottawa	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	Astex Pharmaceuticals, Inc.

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Recommended phase II dose of AT9283	RPTD defined as one dose lower than MTD.	1 year
Primary	Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283	Adverse events graded using NCI CTCAE V3.0	every 3 weeks
Primary	Pharmacokinetic profile of AT9283	PK samples collected on all patients during cycle 1 as described in protocol section 17.2.	cycle one only
Secondary	Efficacy of AT9283	All patients with measurable disease were assessed for response using RECIST criteria as described in protocol section 10.	every 6 weeks