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LymphomaPhase 1NCT00390117

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

A Phase 1 study testing CDKI AT7519 and laboratory biomarker analysis in people with Lymphoma and Unspecified Adult Solid Tumor, Protocol Specific, run by NCIC Clinical Trials Group at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CDKI AT7519 and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
2 sitesCanada
Study dates
5 Jan 2007to 10 Jan 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: 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.

Read the 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.

Being tested
CDKI AT7519, laboratory biomarker analysis
Keywords
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, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma
Medical subject headings
Lymphoma, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma, Follicular, Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CDKI AT7519Drug

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

  • 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.

Study groups in NCT00390117
Study groupRoleWhat they receive
CDKI AT7519ExperimentalAT7519M (1 hour IV) on days 1, 4, 8 and 11 every 5 weeks.
Receives: Drug: CDKI AT7519; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: from time of 1st dose

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

    Measured: from time of 1st dose

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

    during cycle 1

    Measured: one month

  4. Correlation of toxicity profile with pharmacokinetics

    Measured: after completion of each dose level

Secondary outcomes (3)

  1. Preliminary antitumor activity of treatment in patients with measurable disease

    after every second cycle

    Measured: Every 60 days

  2. Overall response (complete and partial response) rate

    after every second cycle

    Measured: Every 60 days

  3. Response duration (median and range)

    Measured: after progression

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Oct 2006 (estimated)
  2. Study start5 Jan 2007
  3. Primary completion13 Mar 2012
  4. Study completion10 Jan 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00390117
Sponsor's protocol ID
I177
Other IDs
CAN-NCIC-IND177, CDR0000507621
Status last verified
Apr 2020
First submitted
18 Oct 2006
Last updated
4 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 25393368

  • 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.

    PubMed 19238148

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CDKI AT7519 and laboratory biomarker analysis in people with Lymphoma and Unspecified Adult Solid Tumor, Protocol Specific, run by NCIC Clinical Trials Group at 2 sites in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose as assessed by NCI CTCAE v.30 (time frame: from time of 1st dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00390117, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2023.

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