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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


Phase 1
2 Years
18 Years
Not Enrolling
Both
Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicities

Safety Issue:

Yes

Principal Investigator

Darren Hargrave, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Royal Marsden NHS Foundation Trust

Authority:

United Kingdom: Medicines and Healthcare Products Regulatory Agency

Study ID:

CDR0000653387

NCT ID:

NCT00985868

Start Date:

September 2009

Completion Date:

December 2012

Related Keywords:

  • Unspecified Childhood Solid Tumor, Protocol Specific
  • unspecified childhood solid tumor, protocol specific
  • Neoplasms

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