Relapsed and refractory solid tumours in children and adolescents MedDRA version: 19.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour System Organ Class: 100000004864
Conditions
Interventions
Product Name: AT9283 (as the free base of the L-lactate salt)
Product Code: AT9283 (as the free base of the L-lactate salt)
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code:
Sponsors
Cancer Research UK
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically proven solid tumour refractory to conventional treatment, or for which no conventional therapy exists. Diffuse Intrinsic Pontine Gliomas that have progressed or relapsed after first line therapy can be included without histological verification if they fulfill the following criteria: At the time of diagnosis a diffuse intrinsic lesion centred in the pons on MRI imaging with a clinical history of 2 to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or chemotherapy during the previous 4 weeks (6 weeks for investigational medicinal products; 2 weeks for vincristine) before treatment. Steroids: Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry. 2. Prior exposure to an Aurora kinase inhibitor. 3. Ongoing toxic manifestations of previous treatments. Exceptions to this are alopecia or certain Grade 1 toxicities, which in the opinion of the Investigator and the Centre for Drug Development (CDD) should not exclude the patient. 4. Pregnant or lactating women are excluded. Female patients with the ability to become pregnant who have a negative serum or urine pregnancy test before enrolment and agree to use two of the following three highly effective forms of combined contraception (oral, injected or implanted hormonal contraception and condom, have a intra-uterine device and condom, diaphragm with spermicidal gel and condom) for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible. 5. Male patients with partners of child-bearing potential (unless they agree to take measures not to father children by using one form of highly effective contraception [condom plus spermicide] during the trial and for six months afterwards). Men with pregnant or lactating partners should be advised to use barrier method contraception (e.g. condom plus spermicidal gel) to prevent exposure to the foetus or neonate. 6. Major thoracic or abdominal surgery from which the patient has not yet recovered. 7. At high medical risk because of non-malignant systemic disease including active uncontrolled infection. 8. Known to be serologically positive for Hepatitis B, Hepatitis C or Human Immunodeficiency Virus (HIV). 9. Fractional shortening of < or = 29% on Echocardiogram 10. LVEF of <50% 11. History of allergy or auto-immune disease*. 12. Congenital heart disease. 13. Prior bone marrow transplant or have had extensive radiotherapy to greater than 25% of bone marrow. 14. Stem Cell Transplant (SCT): Patients who have undergone an autologous stem cell transplant must be greater than three months from the date of the stem cell return. 15. Any other condition which in the Investigator’s opinion would not make the patient a good candidate for the clinical trial. 16. Is a participant or plans to participate in another interventional clinical study, whilst taking part in this Phase I study of AT9283. Participation in an observational study would be acceptable. *this criterion is intended to exlude only those patients with a clinically significant history of allergy or auto-immune disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of AT9283 (given by intravenous (IV) infusion) by characterising the dose limiting toxicities (DLTs) and determining a maximum tolerated dose (MTD) in children and adolescents with relapsed and refractory solid tumours.;Secondary Objective: a) To determine the pharmacokinetics (PK) of AT9283 when administered as an IV infusion in children and adolescents. b) To demonstrate the pharmacodynamic (PD) activity of AT9283 in children and adolescents with relapsed/ refractory malignancy by studying its effects in surrogate tissue. c) To assess preliminary evidence of activity of AT9283 by using appropriate objective tumour measurements in relapsed/ refractory patients with solid tumours (including central nervous system (CNS) tumours). ;Primary end point(s): 1) To determine the Dose Limiting Toxicities (DLT) in children and adolescents with relapsed and refractory solid tumours. 2) To determine the Maximum Tolerated Dose (as defined by a dose below that at which two or more of up to six patients experience DLT) in children and adolescents with relapsed and refractory solid tumours. ;Timepoint(s) of evaluation of this end point: End of trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a) Determining PK parameters and the correlation between them and toxicity and/or efficacy b) Determining magnitude and duration of biomarker change following AT9283 administration (M30 and M65 ELISA) c) Objective tumour responses using RECIST criteria overall, and if possible according to tumour type and bone marrow examinations, plus disease specific biological markers (e.g. Neuroblastoma- MIBG, catecholamines);Timepoint(s) of evaluation of this end point: End of trial | — |
Countries
United Kingdom
Contacts
Public ContactCentre for Drug Development (CDD)
Cancer Research UK
Outcome results
None listed