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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00443976
First received: March 5, 2007
Last updated: January 9, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Non-Hodgkins Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Drug: Aurora kinase inhibitor AT9283
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Maximum tolerated dose of Aurora kinase inhibitor AT9283 (AT9283) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    RPTD defined as one dose lower than MTD.

  • Safety, tolerability, toxicity profile, and dose-limiting toxicity of AT9283 [ Time Frame: every 3 weeks ] [ Designated as safety issue: Yes ]
    Adverse events graded using NCI CTCAE V3.0

  • Pharmacokinetic profile of AT9283 [ Time Frame: cycle one only ] [ Designated as safety issue: No ]
    PK samples collected on all patients during cycle 1 as described in protocol section 17.2.


Secondary Outcome Measures:
  • Efficacy of AT9283 [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]
    All patients with measurable disease were assessed for response using RECIST criteria as described in protocol section 10.


Enrollment: 35
Study Start Date: January 2007
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00443976

Locations
Canada, British Columbia
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Ottawa Health Research Institute - General Division
Ottawa, Ontario, Canada, K1H 8L6
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Karen A. Gelmon, MD British Columbia Cancer Agency
Study Chair: Susan F. Dent, MD Ottawa Regional Cancer Centre
  More Information

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00443976     History of Changes
Other Study ID Numbers: I181, CAN-NCIC-IND181, ASTEX-CAN-NCIC-IND181, CDR0000523837
Study First Received: March 5, 2007
Last Updated: January 9, 2012
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
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

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 23, 2014