Preliminary Anti-tumour Activity of mTor Kinase Inhibitor in Advanced Tumours

Sponsor

AstraZeneca (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT01194193

Collaborator

(none)

Enrollment

Arm

Study Details

Study Description

Brief Summary

To investigate the safety and tolerability of AZD8055 intermittent dosing schedules when given orally to patients with advanced solid malignancies and lymphomas. Two intermittent dosing schedules will be explored with increasing doses until a maximum tolerated dose is determined for each schedule.

Condition or Disease	Intervention/Treatment	Phase
Cancer Advanced Solid Tumours Lymphomas	Drug: AZD8055	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

63 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of the m-Tor Kinase Inhibitor AZD8055 Using Intermittent Dosing Schedules in Patients With Advanced Solid Malignancies and Lymphomas

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: AZD8055 Oral tablet, single dose on Day 1, followed by a 48 hour - 7 day washout and then either twice daily alternate days dosing from multiple dose day 1 onwards or twice daily dosing for 21 days from multiple dose day 1 onwards followed by 7 days no treatment. Cycles of 28 days.

Arm

Intervention/Treatment

Experimental: 1

Drug: AZD8055

Oral tablet, single dose on Day 1, followed by a 48 hour - 7 day washout and then either twice daily alternate days dosing from multiple dose day 1 onwards or twice daily dosing for 21 days from multiple dose day 1 onwards followed by 7 days no treatment. Cycles of 28 days.

Outcome Measures

Primary Outcome Measures

Safety and tolerability of AZD8055; The number of patients with adverse events, including changes in vital signs, general organ function, clinical chemistry, haematology, urinalysis and physical examinations. [Evaluability period is 5 weeks (visit 5), although safety and tolerability parameters will be measured at all visits.]
Safety and tolerability of AZD8055; The number of patients with adverse events, including changes in vital signs, general organ function, clinical chemistry, haematology, urinalysis and physical examinations. [Evaluability period is 5 weeks (visit 6), although safety and tolerability parameters will be measured at all visits.]
Safety and tolerability of AZD8055; The number of patients with adverse events, including changes in vital signs, general organ function, clinical chemistry, haematology, urinalysis and physical examinations. [Evaluability period is 5 weeks (visit 7), although safety and tolerability parameters will be measured at all visits.]
Safety and tolerability of AZD8055; The number of patients with adverse events, including changes in vital signs, general organ function, clinical chemistry, haematology, urinalysis and physical examinations. [Evaluability period is 5 weeks (visit 8), although safety and tolerability parameters will be measured at all visits.]
Safety and tolerability of AZD8055; The number of patients with adverse events, including changes in vital signs, general organ function, clinical chemistry, haematology, urinalysis and physical examinations. [Evaluability period is 5 weeks (visit 9), although safety and tolerability parameters will be measured at all visits.]
Safety and tolerability of AZD8055; The number of patients with adverse events, including changes in vital signs, general organ function, clinical chemistry, haematology, urinalysis and physical examinations. [Evaluability period is 5 weeks (visit 10), although safety and tolerability parameters will be measured at all visits.]
Safety and tolerability of AZD8055; The number of patients with adverse events, including changes in vital signs, general organ function, clinical chemistry, haematology, urinalysis and physical examinations. [Evaluability period is 5 weeks (visit 11), although safety and tolerability parameters will be measured at all visits.]
Safety and tolerability of AZD8055; The number of patients with adverse events, including changes in vital signs, general organ function, clinical chemistry, haematology, urinalysis and physical examinations. [Evaluability period is 5 weeks (visit 12), although safety and tolerability parameters will be measured at all visits.]
Safety and tolerability of AZD8055; The number of patients with adverse events, including changes in vital signs, general organ function, clinical chemistry, haematology, urinalysis and physical examinations. [Evaluability period is 5 weeks (visit 13), although safety and tolerability parameters will be measured at all visits.]
Safety and tolerability of AZD8055; The number of patients with adverse events, including changes in vital signs, general organ function, clinical chemistry, haematology, urinalysis and physical examinations. [Evaluability period is 5 weeks (visit 14), although safety and tolerability parameters will be measured at all visits.]
Evaluate the pharmacokinetics of AZD8055; Pharmacokinetic analysis of the plasma and urine concentration data for AZD8055 and its metabolites will be performed following both single and multiple dosing with two intermittent dosing schedules. [1 cycle (3-4 weeks, at visit 2)]
Evaluate the pharmacokinetics of AZD8055; Pharmacokinetic analysis of the plasma and urine concentration data for AZD8055 and its metabolites will be performed following both single and multiple dosing with two intermittent dosing schedules. [1 cycle (3-4 weeks, at visit 3)]
Evaluate the pharmacokinetics of AZD8055; Pharmacokinetic analysis of the plasma and urine concentration data for AZD8055 and its metabolites will be performed following both single and multiple dosing with two intermittent dosing schedules. [1 cycle (3-4 weeks, at visit 4)]
Evaluate the pharmacokinetics of AZD8055; Pharmacokinetic analysis of the plasma and urine concentration data for AZD8055 and its metabolites will be performed following both single and multiple dosing with two intermittent dosing schedules. [1 cycle (3-4 weeks, at visit 6)]
Evaluate the pharmacokinetics of AZD8055; Pharmacokinetic analysis of the plasma and urine concentration data for AZD8055 and its metabolites will be performed following both single and multiple dosing with two intermittent dosing schedules. [1 cycle (3-4 weeks, at visit 7)]
Evaluate the pharmacokinetics of AZD8055; Pharmacokinetic analysis of the plasma and urine concentration data for AZD8055 and its metabolites will be performed following both single and multiple dosing with two intermittent dosing schedules. [1 cycle (3-4 weeks, at visit 8)]
Evaluate the pharmacokinetics of AZD8055; Pharmacokinetic analysis of the plasma and urine concentration data for AZD8055 and its metabolites will be performed following both single and multiple dosing with two intermittent dosing schedules. [1 cycle (3-4 weeks, at visit 9)]
Evaluate the pharmacokinetics of AZD8055; Pharmacokinetic analysis of the plasma and urine concentration data for AZD8055 and its metabolites will be performed following both single and multiple dosing with two intermittent dosing schedules. [1 cycle (3-4 weeks, at visit 10)]
Evaluate the pharmacokinetics of AZD8055; Pharmacokinetic analysis of the plasma and urine concentration data for AZD8055 and its metabolites will be performed following both single and multiple dosing with two intermittent dosing schedules. [1 cycle (3-4 weeks, at visit 11)]

Secondary Outcome Measures

Preliminary assessment of the anti-tumour activity of AZD8055; Evalution of tumour response using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and percentage change in tumour size and measurement of serological biomarkers. [Every 2 cycles (at visits 1, 17, every subsequent 8 weeks, visit 100]
Investigation of possible relationships between plasma AZD8055 concentrations / exposure and changes in safety parameters (including number and types of adverse events). [1 cycle (3-4 weeks, at visits 2, 3, 4, 6-11)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histological or cytological confirmation of an advanced solid malignant tumour or lymphoma which is refactory to standard therapies or for which no standard therapy exists, patients with measurable or non-measurable disease (according to RECIST criteria)
WHO performance status 0-2
Evidence of post-menopausal status or negative urine/serum pregnancy test for pre-menopausal female patients

Exclusion Criteria:

Patients with severe laboratory abnormalities for haematology, liver or renal function. Also treatment with any haemopoietic growth factors are not allowed within two weeks from first dose of study drug.
Any investigational agents or study drugs from a previous clinical study within 30 days, any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment
Patients with severe cardiac condition of ischemia, impaired ventricular function and arrhythmias, evidence of severe or uncontrolled systemic or current unstable or uncompensated respiratory or cardiac conditions