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

NCT ID: NCT00443976

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-30
• Study Completion Date: 2012-01-06

Brief 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.

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

Conditions

Non-Hodgkins Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AT9283

Group Type: EXPERIMENTAL

Aurora kinase inhibitor AT9283

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astex Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karen A. Gelmon, MD

Role: STUDY_CHAIR

British Columbia Cancer Agency

Susan F. Dent, MD

Role: STUDY_CHAIR

Ottawa Regional Cancer Centre

Locations

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

Ottawa Health Research Institute - General Division

Ottawa, Ontario, Canada

Countries

Canada

References

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.

Reference Type: RESULT

PMID: 24072436 (View on PubMed)

Other Identifiers

CDR0000523837

Identifier Type: REGISTRY

Identifier Source: secondary_id

CAN-NCIC-IND181

Identifier Type: REGISTRY

Identifier Source: secondary_id

ASTEX-CAN-NCIC-IND181

Identifier Type: REGISTRY

Identifier Source: secondary_id

I181

Identifier Type: -

Identifier Source: org_study_id