Advanced solid tumours and lymphomas MedDRA version: 9.1 Level: LLT Classification code 10065143 Term: Malignant solid tumour MedDRA version: 9.1 Level: LLT Classification code 10025632 Term: Malignant lymphoma
Conditions
Interventions
Product Code: AZD8055
Pharmaceutical Form: Oral solution
Product Code: AZD8055
Pharmaceutical Form: Tablet
Sponsors
Astrazeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed written informed consent 2. Male or female, aged 18 years or older 3. Cancer which is refractory to standard therapies, or for which no standard therapies exist, or for which the investigator feels no other active therapy is required for the duration of the study. Inclusion is irrespective of stage of disease. 4. Histological or cytological confirmation of an advanced, solid, malignant tumour (or lymphoma, Part A only). 5. WHO performance status 0-2 (those with performance status 2 must have been stable with no deterioration over the previous 2 weeks) 6. Evidence of post-menopausal status, permanent or surgically sterile, or negative serum or urine pregnancy test for female patients of child-bearing potential. Women will be considered post menopausal if they are over 50 years old and have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments. Permanent sterilisation includes hysterectomy and/or bilateral oopherectomy and/or bilateral salpingectomy but excludes bilateral tubal occlusion. Tubal occlusion is considered a highly effective method of birth control but does not absolutely exclude the possibility of pregnancy. (The term occlusion refers to both occluding and ligating techniques that do not physically remove the oviducts). Women who have undergone tubal occlusion should be managed as if they are of child-bearing potential (eg undergo pregnancy testing as required by the study). Females of reproductive potential are required to use reliable contraception (see Section 3.3.4) 7. For Part A of the study, patients with measurable and non-measurable disease (according to RECIST criteria) can be recruited. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Laboratory values as listed below: (SI Units) - ANC 2.5 x ULN if no demonstrable liver metastases or >5 x ULN in the presence of liver metastases, total bilirubin (TBL) >1.5 x ULN if no demonstrable liver metastases or >3 x ULN in the presence of liver metastases - Serum creatinine >1.5 x ULN or creatinine clearance =50 mL/min (measured or calculated by Cockcroft-Gault method) - Clinically relevant and treatment resistant abnormalities in potassium, sodium, calcium (corrected for plasma albumin) or magnesium 2. Endometrial cancer who have isolated recurrences of their disease (vaginal, pelvic or para-aortic) that are amenable to potentially curative treatment with radiation therapy or surgery 3. Prior chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, corticosteroids or other investigational anti-cancer therapy within 21 days of entering the trial (not including palliative radiotherapy at focal sites). Patients must have also recovered from previous chemo-associated toxicities to Grade 0-1 (with the exception of alopecia). 4. Treatment with any haemopoietic growth factors (eg G-CSF, GM-CSF) within 2 weeks prior to receiving study drug 5. Active spinal cord compression as evidenced by clinical signs and/or oedema or progressive growth demonstrated by imaging unless treated and stable off steroids for at least 1 month prior to study treatment 6. Peripheral neuropathy CTCAE grade > 1 in the past 4 weeks. History of pre-existing leg weakness or muscle diseases 7. Family history of myopathy 8. Past history or current evidence of brain metastases 9. Evidence of severe or uncontrolled systemic conditions (eg, severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardise compliance with the protocol 10. Patients with pre existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome or Renal tubular acidosis 11. Abnormal fasting glucose value defined as >126 mg/dL (> 7 mmol/L). 12. Manifest Diabetes Type I and II or Erythrocyte-HbA1c >6.5% 13. Uncontrolled hypercholesterolaemia or hypertriglyceridaemia (fasting state) despite lipid-lowering therapy 14. Evidence of active infection or active bleeding diatheses 15. Experience of any of the following in the preceding 12 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction (MI), angina pectoris, congestive heart failure NYHA Grade 2, uncontrolled hypertension (BP>150/90 mmHg despite maximal medical management), ventricular arrhythmias requiring continuous therapy, supraventricular arrhythmias including AF, which are uncontrolled, haemorrhagic or thrombotic stroke, including transient ischaemic attacks or any other central nervous system bleeding 16. Abnormal echocardiogram at baseline (LVEF 450ms from 3 ECGs using Fridericia's correction at both screening visit and predose on the first day of dosing 19. Patients taking concomitant medications known to prolong QT interval or with factors that increase the risk of QT prolongation or arrhythmic events (heart failure, hyperka
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety and tolerability of AZD8055 in patients with advanced solid tumours (or lymphomas Part A only).;Secondary Objective: 1. To determine the pharmacokinetics of AZD8055 following both single and multiple oral dosing of AZD8055 in patients with advanced solid tumours (or lymphomas Part A only). 2. To obtain a preliminary evaluation of the role of renal excretion in the disposition of AZD8055. 3. To evaluate phosphorylation levels of biomarkers such as, but not limited to, AKT and 4EBP1 following treatment with AZD8055 in PBMCs. 4. To investigate possible relationships between plasma AZD8055 concentrations/exposure and changes in safety and pharmacodynamic (PD) parameters. 5. To give an early indication of efficacy by evaluation of tumour size. 6. To determine inhibition of tumour glucose uptake by assessment with FDG-PET (Part A only). ;Primary end point(s): Safety and tolerability: Assessed by incidence and severity of adverse events (CTCAE Version 3.0), vital signs, general organ function, clinical chemistry (including liver function test), haematology and urinalysis, coagulation, glucose management, ECG and echocardiography, nervous and musculoskeletal system examination. | — |
Countries
France, United Kingdom
Outcome results
None listed