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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00390117
First received: October 18, 2006
Last updated: January 10, 2013
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Drug: CDKI AT7519
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of AT7519M Given Twice Weekly 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 as assessed by NCI CTCAE v.30 [ Time Frame: from time of 1st dose ] [ Designated as safety issue: Yes ]
  • Safety, tolerability, toxicity profile, and dose-limiting toxicities as assessed by NCI CTCAE v.30 [ Time Frame: from time of 1st dose ] [ Designated as safety issue: Yes ]
  • Pharmacokinetic profile as measured on days 1, 2, and 4 in course 1 [ Time Frame: one month ] [ Designated as safety issue: No ]
    during cycle 1

  • Correlation of toxicity profile with pharmacokinetics [ Time Frame: after completion of each dose level ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Preliminary antitumor activity of treatment in patients with measurable disease [ Time Frame: Every 60 days ] [ Designated as safety issue: No ]
    after every second cycle

  • Overall response (complete and partial response) rate [ Time Frame: Every 60 days ] [ Designated as safety issue: No ]
    after every second cycle

  • Response duration (median and range) [ Time Frame: after progression ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: August 2006
Study Completion Date: January 2013
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  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

      • 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
  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: NCT00390117

Locations
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Sebastien Hotte, MD Margaret and Charles Juravinski Cancer Centre
Study Chair: Eric X. Chen, MD, PhD Princess Margaret Hospital, Canada
  More Information

Additional Information:
No publications provided by NCIC Clinical Trials Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00390117     History of Changes
Other Study ID Numbers: I177, CAN-NCIC-IND177, CDR0000507621
Study First Received: October 18, 2006
Last Updated: January 10, 2013
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
unspecified adult solid tumor, protocol specific
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
Waldenstrom macroglobulinemia
recurrent adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

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

ClinicalTrials.gov processed this record on September 18, 2014