A Phase I/II, Open Label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Tor Kinase Inhibitor AZD8055 Administered Orally to Patients with Advanced Solid Tumours, Lymphomas and Endometrial Carcinoma

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2008-002606-18-FR
• Date of registration: 29/07/2008
• Prospective Registration: Yes
• Primary sponsor: Astrazeneca AB
• Public title: A Phase I/II, Open Label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Tor Kinase Inhibitor AZD8055 Administered Orally to Patients with Advanced Solid Tumours, Lymphomas and Endometrial Carcinoma
• Scientific title: A Phase I/II, Open Label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the Tor Kinase Inhibitor AZD8055 Administered Orally to Patients with Advanced Solid Tumours, Lymphomas and Endometrial Carcinoma
• Date of first enrolment: 03/11/2008
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-002606-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, United Kingdom

Key inclusion & exclusion 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. Patients with endometrial carcinosarcomas can be included in the study but will be analysed in the non-endometrial sub group in Part B.
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 Parts A and B 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:
1. Laboratory values as listed below: (SI Units)
- ANC <1.5x109/L
- Platelets <100x109/L
- Haemoglobin (Hb) <9.0 g/dL
- AST (SGOT) or ALT (SGPT) >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
- Proteinuria +1 on dipstick analysis or >500 mg/24 hours
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.
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. History of peripheral neuropathy, 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. Impaired oral glucose tolerance test (OGTT) as defined by fasting glucose >109 mg/dL (6.1 mmol/L) and postprandial glucose 2h level >140mg/dL (>7.8 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 < 55% and shortening fraction SF <15%)
17. Torsades de Pointes, currently or within 2 weeks of study entry
18. Patients with mean QTc interval >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 in

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Advanced solid tumours, lymphomas and endometrial carcinoma
MedDRA version: 9.1 Level: LLT Classification code 10014733 Term: Endometrial cancer
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

Intervention(s)

Product Code: AZD8055
Pharmaceutical Form: Oral solution

Primary Outcome(s)

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.

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 (including 20 patients with endometrial carcinoma in Part B).
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 AKT following treatment with AZD8055.
4. To investigate possible relationships between plasma AZD8055 concentrations/exposure and changes in safety and 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.

Main Objective: To assess the safety and tolerability of AZD8055 in patients with advanced solid tumours or lymphomas (including 20 patients with endometrial carcinoma in Part B).

Secondary ID(s)

2008-002606-18-GB

D1600C00001

Ethics review

Status: Approved
Approval date: 03/11/2008
Contact:

Results

• Results available: Yes
• Date Posted: 30/09/2016
• Date Completed: 29/11/2010
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-002606-18/results