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AT7519M in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00390117
Recruitment Status : Completed
First Posted : October 19, 2006
Last Update Posted : April 8, 2020
Sponsor:
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

Tracking Information
First Submitted Date  ICMJE October 18, 2006
First Posted Date  ICMJE October 19, 2006
Last Update Posted Date April 8, 2020
Actual Study Start Date  ICMJE August 22, 2006
Actual Primary Completion Date March 13, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2011)
  • Maximum tolerated dose as assessed by NCI CTCAE v.30 [ Time Frame: from time of 1st dose ]
  • Safety, tolerability, toxicity profile, and dose-limiting toxicities as assessed by NCI CTCAE v.30 [ Time Frame: from time of 1st dose ]
  • Pharmacokinetic profile as measured on days 1, 2, and 4 in course 1 [ Time Frame: one month ]
    during cycle 1
  • Correlation of toxicity profile with pharmacokinetics [ Time Frame: after completion of each dose level ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2011)
  • Preliminary antitumor activity of treatment in patients with measurable disease [ Time Frame: Every 60 days ]
    after every second cycle
  • Overall response (complete and partial response) rate [ Time Frame: Every 60 days ]
    after every second cycle
  • Response duration (median and range) [ Time Frame: after progression ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AT7519M in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory Non-Hodgkin's Lymphoma
Official Title  ICMJE A Phase I Study of AT7519M Given Twice Weekly in Patients With Advanced Incurable Malignancy
Brief Summary

RATIONALE: AT7519M 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 AT7519M in treating patients with advanced or metastatic solid tumors or refractory non-Hodgkin's lymphoma.

Detailed Description

OBJECTIVES:

Primary

  • Determine the recommended phase II dose of AT7519M in patients with advanced or metastatic solid tumors or refractory non-Hodgkin's lymphoma.
  • Determine the safety, tolerability, toxicity profile, and dose-limiting toxicities of this drug in these patients.
  • Determine the pharmacokinetic profile of this drug in these patients.
  • Correlate the toxicity profile with pharmacokinetics of this drug in these patients.

Secondary

  • Assess, preliminarily, the antitumor activity of this drug in these patients.

OUTLINE: This is an open-label, dose-escalation, multicenter study.

Patients receive AT7519M IV over 1-3 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of AT7519M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during course 1. Once the MTD has been determined, up to 8 additional patients are treated at the MTD.

Patients undergo blood collection periodically for pharmacokinetic studies. Patients treated at the MTD also undergo tumor tissue biopsies or aspirates and blood collection periodically for additional pharmacodynamic and correlative biomarker studies.

After completion of study therapy, patients are followed at 4 weeks. Patients with complete response, partial response, or stable disease are followed every 3 months thereafter until relapse.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
Intervention  ICMJE
  • Drug: CDKI AT7519
    AT7519M (1 hour IV) on days 1, 4, 8 and 11 every 5 weeks.
  • Other: laboratory biomarker analysis
    Pharmacokinetic bioanalysis of the AT7519 plasma concentration data will be performed by BioDynamics Northhampton, U.K. The pharmacokinetic parameters for AT7519 will be determined by Astex Therapeutics as data permits.
Study Arms  ICMJE Experimental: CDKI AT7519
AT7519M (1 hour IV) on days 1, 4, 8 and 11 every 5 weeks.
Interventions:
  • Drug: CDKI AT7519
  • Other: laboratory biomarker analysis
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 2, 2012)
34
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE January 10, 2013
Actual Primary Completion Date March 13, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed diagnosis of 1 of the following:

    • Advanced and/or metastatic solid tumor

      • No more than 3 prior regimens for metastatic disease
    • Refractory non-Hodgkin's lymphoma
  • Clinically or radiologically documented disease

    • Patients whose only evidence of disease is tumor marker elevation are not eligible
  • No untreated brain or meningeal metastases

    • Patients with radiologic or clinical evidence of stable, treated brain metastases are eligible provided they are asymptomatic AND have no requirement for corticosteroids

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 patient has documented liver metastases)
  • Potassium normal
  • Calcium normal
  • Creatine kinase (CK or CPK) ≤ 2 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction, including any of the following:

    • Significant cardiac event (including symptomatic heart failure or angina) within the past 3 months or any cardiac disease that, in the opinion of the investigator, increases the risk for ventricular arrhythmia
    • Any history of ventricular arrhythmia, which was symptomatic or required treatment (CTC grade 3), including multifocal PVCs, bigeminy, trigeminy, or ventricular tachycardia
    • Uncontrolled hypertension
    • Previous history of QT prolongation with other medication
    • Congenital long QT syndrome
    • QT and QTc, with Bazett's correction, unmeasurable or ≥ 460 msec on screening ECG
    • LVEF < 45 % by MUGA for patients with significant cardiac history (i.e., myocardial infarction, severe hypertension, or arrhythmia) or prior doxorubicin (> 450 mg/m²)
  • No active or uncontrolled infections
  • No serious illness or medical condition that would preclude study compliance
  • No peripheral neuropathy > grade 1

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 21 days since prior cytotoxic chemotherapy and recovered (solid tumors)
  • At least 21 days since prior palliative radiotherapy and recovered

    • Exceptions may be made for low-dose, nonmyelosuppressive radiotherapy
  • Prior hormonal, immunologic, biologic, or signal transduction inhibitor therapy allowed
  • At least 14 days since prior major surgery and recovered (no nonhealing wounds)
  • At least 4 weeks since prior steroids
  • No other concurrent medications which affect QT/QTc and cannot be discontinued
  • No other concurrent experimental drugs or anticancer therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00390117
Other Study ID Numbers  ICMJE I177
CAN-NCIC-IND177 ( Registry Identifier: NCI US - Physician Data Query )
CDR0000507621 ( Other Identifier: PDQ )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Canadian Cancer Trials Group ( NCIC Clinical Trials Group )
Study Sponsor  ICMJE NCIC Clinical Trials Group
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Sebastien Hotte, MD Margaret and Charles Juravinski Cancer Centre
Study Chair: Eric X. Chen, MD, PhD Princess Margaret Hospital, Canada
PRS Account Canadian Cancer Trials Group
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP