NCT00390117

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at P50-P75 for phase_1 lymphoma

Timeline
Completed

Started Jan 2007

Typical duration for phase_1 lymphoma

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 18, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 19, 2006

Completed
3 months until next milestone

Study Start

First participant enrolled

January 5, 2007

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 13, 2012

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 10, 2013

Completed
Last Updated

August 4, 2023

Status Verified

April 1, 2020

Enrollment Period

5.2 years

First QC Date

October 18, 2006

Last Update Submit

August 3, 2023

Conditions

LymphomaUnspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specificrecurrent adult Burkitt lymphomarecurrent adult diffuse large cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomaWaldenstrom macroglobulinemiarecurrent adult grade III lymphomatoid granulomatosisadult nasal type extranodal NK/T-cell lymphomanodal marginal zone B-cell lymphomasplenic marginal zone lymphoma

Outcome Measures

Primary Outcomes (4)

  • Maximum tolerated dose as assessed by NCI CTCAE v.30

    from time of 1st dose

  • Safety, tolerability, toxicity profile, and dose-limiting toxicities as assessed by NCI CTCAE v.30

    from time of 1st dose

  • Pharmacokinetic profile as measured on days 1, 2, and 4 in course 1

    during cycle 1

    one month

  • Correlation of toxicity profile with pharmacokinetics

    after completion of each dose level

Secondary Outcomes (3)

  • Preliminary antitumor activity of treatment in patients with measurable disease

    Every 60 days

  • Overall response (complete and partial response) rate

    Every 60 days

  • Response duration (median and range)

    after progression

Study Arms (1)

CDKI AT7519

EXPERIMENTAL

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

Drug: CDKI AT7519Other: laboratory biomarker analysis

Interventions

CDKI AT7519DRUG

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

CDKI AT7519
laboratory biomarker analysisOTHER

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.

CDKI AT7519

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (2)

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (2)

  • Chen EX, Hotte S, Hirte H, Siu LL, Lyons J, Squires M, Lovell S, Turner S, McIntosh L, Seymour L. A Phase I study of cyclin-dependent kinase inhibitor, AT7519, in patients with advanced cancer: NCIC Clinical Trials Group IND 177. Br J Cancer. 2014 Dec 9;111(12):2262-7. doi: 10.1038/bjc.2014.565. Epub 2014 Nov 13.

    PMID: 25393368RESULT

  • Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009 Mar;9(3):153-66. doi: 10.1038/nrc2602.

    PMID: 19238148DERIVED

MeSH Terms

Conditions

LymphomaBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, FollicularLymphoma, Mantle-CellLymphoma, B-Cell, Marginal ZoneLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom MacroglobulinemiaLymphoma, Extranodal NK-T-Cell

Interventions

4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxylic acid piperidin-4-ylamide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersLymphoma, T-Cell

Study Officials

  • Sebastien Hotte, MD

    Margaret and Charles Juravinski Cancer Centre

    STUDY CHAIR

  • Eric X. Chen, MD, PhD

    Princess Margaret Hospital, Canada

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 18, 2006

First Posted

October 19, 2006

Study Start

January 5, 2007

Primary Completion

March 13, 2012

Study Completion

January 10, 2013

Last Updated

August 4, 2023

Record last verified: 2020-04

Data Sharing

IPD Sharing
Will not share

Locations

CA(2)