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AT9283 in Children and Adolescents With Relapsed and Refractory Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cancer Research UK
ClinicalTrials.gov Identifier:
NCT00985868
First received: September 26, 2009
Last updated: April 17, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: multikinase inhibitor AT9283
Other: enzyme-linked immunosorbent assay
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Cancer Research UK:

Primary Outcome Measures:
  • Dose-limiting toxicities [ Designated as safety issue: Yes ]
  • Maximum-tolerated dose [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetic parameters and the correlation between them and toxicity and/or efficacy [ Designated as safety issue: No ]
  • The magnitude and duration of biomarkers (M30 and M65 ELISA) change after AT9283 administration [ Designated as safety issue: No ]
  • Objective tumor response according to RECIST criteria [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: September 2009
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
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.

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.

  Eligibility

Ages Eligible for Study:   2 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00985868

Locations
United Kingdom
Birmingham Children's Hospital
Birmingham, England, United Kingdom, B4 6NH
Leeds General Infirmary
Leeds, England, United Kingdom, LS9 7TF
Royal Manchester Children's Hospital
Manchester, England, United Kingdom, M27 4HA
Great North Children's Hospital, Royal Victoria Infirmary
Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Sponsors and Collaborators
Cancer Research UK
Investigators
Principal Investigator: Darren Hargrave, MD Royal Marsden NHS Foundation Trust
  More Information

Additional Information:
No publications provided

Responsible Party: Cancer Research UK
ClinicalTrials.gov Identifier: NCT00985868     History of Changes
Other Study ID Numbers: CDR0000653387, UKM-ICRF-CR0708-11, CRUK-CR0708-11, EUDRACT-2008-005542-23, EU-20980
Study First Received: September 26, 2009
Last Updated: April 17, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Cancer Research UK:
unspecified childhood solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on November 27, 2014