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

This study has been withdrawn prior to enrollment.
(Amendment to study compound development programme)
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01194193
First received: August 18, 2010
Last updated: May 13, 2011
Last verified: May 2011
  Purpose

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 Intervention Phase
Cancer
Advanced Solid Tumours
Lymphomas
Drug: AZD8055
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

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. [ Time Frame: Evaluability period is 5 weeks (visit 5), although safety and tolerability parameters will be measured at all visits. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Evaluability period is 5 weeks (visit 6), although safety and tolerability parameters will be measured at all visits. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Evaluability period is 5 weeks (visit 7), although safety and tolerability parameters will be measured at all visits. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Evaluability period is 5 weeks (visit 8), although safety and tolerability parameters will be measured at all visits. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Evaluability period is 5 weeks (visit 9), although safety and tolerability parameters will be measured at all visits. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Evaluability period is 5 weeks (visit 10), although safety and tolerability parameters will be measured at all visits. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Evaluability period is 5 weeks (visit 11), although safety and tolerability parameters will be measured at all visits. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Evaluability period is 5 weeks (visit 12), although safety and tolerability parameters will be measured at all visits. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Evaluability period is 5 weeks (visit 13), although safety and tolerability parameters will be measured at all visits. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: Evaluability period is 5 weeks (visit 14), although safety and tolerability parameters will be measured at all visits. ] [ Designated as safety issue: Yes ]
  • 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. [ Time Frame: 1 cycle (3-4 weeks, at visit 2) ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 cycle (3-4 weeks, at visit 3) ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 cycle (3-4 weeks, at visit 4) ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 cycle (3-4 weeks, at visit 6) ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 cycle (3-4 weeks, at visit 7) ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 cycle (3-4 weeks, at visit 8) ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 cycle (3-4 weeks, at visit 9) ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 cycle (3-4 weeks, at visit 10) ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: 1 cycle (3-4 weeks, at visit 11) ] [ Designated as safety issue: No ]

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. [ Time Frame: Every 2 cycles (at visits 1, 17, every subsequent 8 weeks, visit 100 ] [ Designated as safety issue: No ]
  • Investigation of possible relationships between plasma AZD8055 concentrations / exposure and changes in safety parameters (including number and types of adverse events). [ Time Frame: 1 cycle (3-4 weeks, at visits 2, 3, 4, 6-11) ] [ Designated as safety issue: No ]

Estimated Enrollment: 63
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01194193

Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Ian Smith, MD AstraZeneca R&D
  More Information

No publications provided

Responsible Party: MSD, AstraZeneca
ClinicalTrials.gov Identifier: NCT01194193     History of Changes
Other Study ID Numbers: D1600C00002
Study First Received: August 18, 2010
Last Updated: May 13, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by AstraZeneca:
Cancer
Advanced solid tumours
lymphomas
dose escalation
preliminary anti-tumour activity
Tor kinase inhibitor
oral administration
intermittent dosing

Additional relevant MeSH terms:
Lymphoma
Neoplasms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 20, 2014