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

August 3, 2023 updated by: NCIC Clinical Trials Group

A Phase I Study of AT7519M Given Twice Weekly in Patients With Advanced Incurable Malignancy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

34

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
    • Ontario
      • Hamilton, Ontario, Canada, L8V 5C2
        • Juravinski Cancer Centre at Hamilton Health Sciences
      • Toronto, Ontario, Canada, M5G 2M9
        • Univ. Health Network-Princess Margaret Hospital

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

      • 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

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: CDKI AT7519
AT7519M (1 hour IV) on days 1, 4, 8 and 11 every 5 weeks.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose as assessed by NCI CTCAE v.30
Time Frame: from time of 1st dose
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
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
one month
Correlation of toxicity profile with pharmacokinetics
Time Frame: after completion of each dose level
after completion of each dose level

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Preliminary antitumor activity of treatment in patients with measurable disease
Time Frame: Every 60 days
after every second cycle
Every 60 days
Overall response (complete and partial response) rate
Time Frame: Every 60 days
after every second cycle
Every 60 days
Response duration (median and range)
Time Frame: after progression
after progression

Collaborators and Investigators

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

Sponsor

NCIC Clinical Trials Group

Investigators

  • Study Chair: Eric X. Chen, MD, PhD, Princess Margaret Hospital, Canada
  • Study Chair: Sebastien Hotte, MD, Margaret and Charles Juravinski Cancer Centre

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 5, 2007

Primary Completion (Actual)

March 13, 2012

Study Completion (Actual)

January 10, 2013

Study Registration Dates

First Submitted

October 18, 2006

First Submitted That Met QC Criteria

October 18, 2006

First Posted (Estimated)

October 19, 2006

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

  • I177
  • CAN-NCIC-IND177 (Registry Identifier: NCI US - Physician Data Query)
  • CDR0000507621 (Other Identifier: PDQ)

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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