Dose Limiting Toxicities (DLT) Sample Clauses

Dose Limiting Toxicities (DLT). An AE or laboratory abnormality considered to be related to paclitaxel, that commences at any time during the DLT evaluation period (Cycle 1, comprises a 28-day evaluation period) and meets either of the following criteria • Requires a dose reduction or omission to <60% of the intended Cycle 1 total paclitaxel dose (90 mg/m2 x 3). • Any delay to the administration of weekly paclitaxel chemotherapy on D1 of Cycle 2 by ≥7 days as a consequence of paclitaxel induced toxicity A DLT is defined as an AE or laboratory abnormality considered to be related to AZD5363 that commences at any time during the DLT evaluation period (Cycle 1) which includes: • Haematological toxicity: o CTCAE grade 4 haematological toxicity of any duration o Febrile neutropenia (CTCAE grade ≥3 with temperature ≥38.5°C which is unresponsive to antipyretics) o CTCAE grade ≥3 neutropenia requiring hospitalisation o CTCAE grade ≥3 thrombocytopenia associated with non-traumatic bleeding (but not applicable to patients on therapeutic anticoagulation) • Clinical chemistry toxicity: o CTCAE ≥ Grade 3 hyperglycaemia (glucose >13.9 mmol/L) for more than 1 week, despite optimal intervention which is not attributable to another co- morbidity o Grade 4 hyperglycaemia (glucose >27.8 mmol/L) o AST or ALT >10x ULN and AZD5363 is considered the most likely cause o AST or ALT >8x ULN, when combined with doubling of bilirubin from baseline, and AZD5363 is considered the most likely cause • Cardiovascular toxicity: o QTc (Xxxxxxxxxx's or Bazett's correction) interval > 500 msec or QTc increase >60 msec from baseline on two ECGs at least 30 minutes apart, that cannot be attributed to another cause o Symptomatic congestive cardiac failure (New York Heart Association [NYHA] class III/IV) and a d rop in left ventricular ejection fraction (LVEF) which cannot be attributed to another cause. N ote: Concomitant use of vasotonic drugs, adrenergic blockers, negative inotropic agents and anti-hypertensives should be taken into consideration when assigning causality. o A decrease in LVEF of ≥20% to a level below the institution's lower limit of normal range o CTCAE grade ≥3 hypotension which cannot be attributed to another cause • Other toxicities: o Clinically significant rash that despite optimal treatment remains CTCAE grade ≥3 for 5 days or longer and that cannot be attributed to another cause o CTCAE grade ≥3 nausea, vomiting or diarrhoea, despite optimal anti-emetic or anti-diarrhoeal therapy, and which cannot be ...