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

NCT01194193 | Withdrawn Phase 1

• 1 other identifier: D1600C00002
• Study Type: interventional
• Target: 63
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Cancer; Advanced Solid Tumours; Lymphomas

Keywords

Cancer; Advanced solid tumours; lymphomas; dose escalation; preliminary anti-tumour activity; Tor kinase inhibitor; oral administration; intermittent dosing

Outcome Measures

Primary Outcomes (19)

• 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 Outcomes (2)

• 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)

Study Arms (1)

1

EXPERIMENTAL

Drug: AZD8055

Interventions

AZD8055 DRUG

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.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

MeSH Terms

Conditions

Neoplasms; Lymphoma

Interventions

(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Ian Smith, MD

  AstraZeneca R&D

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 18, 2010
• First Posted: September 2, 2010
• Last Updated: May 16, 2011

Record last verified: 2011-05