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AT9283 in Children and Adolescents With Relapsed and Refractory Solid Tumors

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: NCT00985868
Recruitment Status : Completed
First Posted : September 29, 2009
Last Update Posted : November 29, 2019
Sponsor:
Information provided by (Responsible Party):
Cancer Research UK

Tracking Information
First Submitted Date  ICMJE September 26, 2009
First Posted Date  ICMJE September 29, 2009
Last Update Posted Date November 29, 2019
Study Start Date  ICMJE September 2009
Actual Primary Completion Date January 25, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 26, 2009)
  • Dose-limiting toxicities
  • Maximum-tolerated dose
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 26, 2009)
  • Pharmacokinetic parameters and the correlation between them and toxicity and/or efficacy
  • The magnitude and duration of biomarkers (M30 and M65 ELISA) change after AT9283 administration
  • Objective tumor response according to RECIST criteria
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AT9283 in Children and Adolescents With Relapsed and Refractory Solid Tumors
Official Title  ICMJE A CCLG/Cancer Research UK Phase I Trial of AT9283 (a Selective Inhibitor of Aurora Kinases) Given for 72 Hours Every 21 Days Via Intravenous Infusion in Children and Adolescents With Relapsed and Refractory Solid Tumors
Brief Summary

RATIONALE: AT9283 may stop the growth of tumor 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 AT9283 in children and adolescents with relapsed and refractory solid tumors.

Detailed Description

OBJECTIVES:

Primary

  • To evaluate the safety and tolerability of Aurora kinase inhibitor AT9283 by characterizing the dose-limiting toxicities in children and adolescents with relapsed and refractory solid tumors.
  • To determine the maximum-tolerated dose of this regimen in these patients.

Secondary

  • To determine the pharmacokinetic parameters of this regimen in these patients.
  • To demonstrate the pharmacodynamic (PD) activity of this regimen in these patients by studying its effects in surrogate tissue.
  • To assess preliminary evidence of activity of this regimen by using appropriate objective tumor measurements in these patients.

Tertiary

  • To demonstrate the PD activity of this regimen in these patients by studying its effects in both surrogate and tumor tissue (skin punch, bone marrow, and tumor biopsies).

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive Aurora kinase inhibitor AT9283 IV over 72 hours on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.If a patient is benefiting from treatment with AT9283 (i.e. has stable or responding disease as measured by RECIST) and the benefit risk balance is considered acceptable then further treatment may be given.

Blood and skin tissue samples are collected at baseline and periodically during treatment for pharmacokinetic studies and pharmacodynamic and biomarker (M30, M65, pHH53, p53, PCNA and Ki67) analysis by IHC and ELISA assays.

After completion of study therapy, patients are followed up periodically.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Unspecified Childhood Solid Tumor, Protocol Specific
Intervention  ICMJE
  • Drug: multikinase inhibitor AT9283
  • Other: enzyme-linked immunosorbent assay
  • Other: immunohistochemistry staining method
  • Other: laboratory biomarker analysis
  • Other: pharmacological study
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   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 23, 2018)
33
Original Estimated Enrollment  ICMJE
 (submitted: September 26, 2009)
24
Actual Study Completion Date  ICMJE November 20, 2019
Actual Primary Completion Date January 25, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed solid tumor meeting 1 of the following criteria:

    • Refractory to conventional treatment
    • Disease for which no conventional therapy exists
  • Patients with CNS tumors must be on a stable or decreasing dose of dexamethasone for ≥ 1 week before study entry

PATIENT CHARACTERISTICS:

  • WHO performance status (PS) 0-2 OR Lansky Play PS 70-100% (> 50% is acceptable if it is due to a stable neurological deficit or CNS tumor)
  • Life expectancy ≥ 12 weeks
  • ANC ≥ 1,000/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL
  • Serum bilirubin < 1.5 times upper limit of normal (ULN)
  • Creatinine kinase normal
  • ALT or AST < 2.5 times ULN (≤ 5 times ULN if due to tumor)
  • Creatinine clearance/EDTA-measured GFR ≥ 60 mL/min
  • Sufficient blood volume to undergo the blood-sampling regimen specified by the protocol that, in the opinion of the investigator, will not jeopardize patient's safety
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use 2 methods of effective contraception 4 weeks before, during, and for 6 months after completion of study therapy
  • Not at high medical risk because of non-malignant systemic disease, including active uncontrolled infection
  • Not known to be serologically positive for hepatitis B or C or HIV
  • Fractional shortening of > 29% on echocardiogram
  • LVEF ≥ 50%
  • No history of allergy or auto-immune disease
  • No congenital heart disease
  • No other condition that, in the investigator's opinion, would not make the patient a good candidate for the clinical trial

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from prior therapy
  • More than 4 weeks since prior radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, or chemotherapy (6 weeks for investigational medicinal products, 2 weeks for vincristine)
  • More than 3 months since prior autologous stem cell transplantation
  • No prior allogenic bone marrow transplantation
  • No prior extensive radiotherapy to > 25% of bone marrow
  • No prior Aurora kinase inhibitor
  • No prior major thoracic or abdominal surgery from which the patient has not yet recovered
  • No prior or concurrent participation in another interventional clinical trial

    • Participation in an observational study allowed
  • No other concurrent anticancer therapy or investigational drugs
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00985868
Other Study ID Numbers  ICMJE CDR0000653387
UKM-ICRF-CR0708-11
CRUK-CR0708-11
EUDRACT-2008-005542-23
EU-20980
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cancer Research UK
Study Sponsor  ICMJE Cancer Research UK
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Darren Hargrave, MD Great Ormond Street Hospital for Children NHS Foundation Trust
PRS Account Cancer Research UK
Verification Date November 2019

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