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

Primary Purpose

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

Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Aurora kinase inhibitor AT9283
Sponsored by
NCIC Clinical Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkins Lymphoma focused on measuring 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, 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • BCCA - Vancouver Cancer Centre
  • Ottawa Health Research Institute - General Division

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

AT9283

Arm Description

Outcomes

Primary Outcome Measures

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).
Recommended phase II dose of AT9283
RPTD defined as one dose lower than MTD.
Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283
Adverse events graded using NCI CTCAE V3.0
Pharmacokinetic profile of AT9283
PK samples collected on all patients during cycle 1 as described in protocol section 17.2.

Secondary Outcome Measures

Efficacy of AT9283
All patients with measurable disease were assessed for response using RECIST criteria as described in protocol section 10.

Full Information

First Posted
March 5, 2007
Last Updated
August 3, 2023
Sponsor
NCIC Clinical Trials Group
Collaborators
Astex Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00443976
Brief Title
Aurora Kinase Inhibitor AT9283 in Treating Patients With Advanced or Metastatic Solid Tumors or Non-Hodgkin's Lymphoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
January 30, 2007 (Actual)
Primary Completion Date
April 9, 2010 (Actual)
Study Completion Date
January 6, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NCIC Clinical Trials Group
Collaborators
Astex Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkins Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific
Keywords
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, 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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AT9283
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Aurora kinase inhibitor AT9283
Intervention Description
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.
Primary Outcome Measure Information:
Title
Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283)
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).
Time Frame
1 year
Title
Recommended phase II dose of AT9283
Description
RPTD defined as one dose lower than MTD.
Time Frame
1 year
Title
Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283
Description
Adverse events graded using NCI CTCAE V3.0
Time Frame
every 3 weeks
Title
Pharmacokinetic profile of AT9283
Description
PK samples collected on all patients during cycle 1 as described in protocol section 17.2.
Time Frame
cycle one only
Secondary Outcome Measure Information:
Title
Efficacy of AT9283
Description
All patients with measurable disease were assessed for response using RECIST criteria as described in protocol section 10.
Time Frame
every 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen A. Gelmon, MD
Organizational Affiliation
British Columbia Cancer Agency
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Susan F. Dent, MD
Organizational Affiliation
Ottawa Regional Cancer Centre
Official's Role
Study Chair
Facility Information:
Facility Name
BCCA - Vancouver Cancer Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 4E6
Country
Canada
Facility Name
Ottawa Health Research Institute - General Division
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
24072436
Citation
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.
Results Reference
result

Learn more about this trial

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

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