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

August 3, 2023 updated by: NCIC Clinical Trials Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BCCA - Vancouver Cancer Centre
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Health Research Institute - General Division

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AT9283
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283)
Time Frame: 1 year
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
Recommended phase II dose of AT9283
Time Frame: 1 year
RPTD defined as one dose lower than MTD.
1 year
Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283
Time Frame: every 3 weeks
Adverse events graded using NCI CTCAE V3.0
every 3 weeks
Pharmacokinetic profile of AT9283
Time Frame: cycle one only
PK samples collected on all patients during cycle 1 as described in protocol section 17.2.
cycle one only

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of AT9283
Time Frame: every 6 weeks
All patients with measurable disease were assessed for response using RECIST criteria as described in protocol section 10.
every 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

NCIC Clinical Trials Group

Collaborators

Astex Pharmaceuticals, Inc.

Investigators

  • Study Chair: Susan F. Dent, MD, Ottawa Regional Cancer Centre
  • Study Chair: Karen A. Gelmon, MD, British Columbia Cancer Agency

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 30, 2007

Primary Completion (Actual)

April 9, 2010

Study Completion (Actual)

January 6, 2012

Study Registration Dates

First Submitted

March 5, 2007

First Submitted That Met QC Criteria

March 5, 2007

First Posted (Estimated)

March 7, 2007

Study Record Updates

Last Update Posted (Actual)

August 4, 2023

Last Update Submitted That Met QC Criteria

August 3, 2023

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I181
  • CDR0000523837 (Registry Identifier: PDQ)
  • CAN-NCIC-IND181 (Registry Identifier: NCI US - Physician Data Query)
  • ASTEX-CAN-NCIC-IND181 (Registry Identifier: Astex Therapeutics Inc.)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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