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Study to Assess the Safety and Preliminary Efficacy of AZD0156 at Increasing Doses Alone or in Combination With Other Anti-cancer Treatment in Patients With Advanced Cancer (AToM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by AstraZeneca
Sponsor:
Collaborator:
INC Research
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT02588105
First received: October 19, 2015
Last updated: January 19, 2017
Last verified: January 2017
  Purpose
The purpose of this study is to determine whether AZD0156 is safe, what is the best dose to give, and how it is processed by the body when given alone or in combination with other agents. The study will also collect some initial information about how effective it is.

Condition Intervention Phase
Advanced Solid Tumours
Drug: AZD0156
Drug: Olaparib
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Ascending Doses of AZD0156 Monotherapy or in Combination With Either Cytotoxic Chemotherapies or Novel Anti-Cancer Agents in Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Safety and tolerability - Number of patients experiencing adverse events [ Time Frame: Informed consent until end of Safety Follow-up (approximately 6 months) ]
    Safety and tolerability of AZD0156 alone or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents as assessed through collection of Adverse Event, Serious Adverse Event, Clinical Chemistry/Haematology/Coagulation/Vital Signs and ECG


Secondary Outcome Measures:
  • Anti-tumour activity assessed through tumour measurements [ Time Frame: Baseline and then every 6 weeks until Safety follow-up (approximately 6 months) ]
    Preliminary assessment of the anti-tumour activity of AZD0156 either as monotherapy alone or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents by evaluation of tumour response objective response rate using RECIST version 1.1

  • Changes in expression levels of proteins that may be impacted by ATM protein activity or inhibition [ Time Frame: From baseline until 21 days of combination therapy (Approximately 11 assessments) ]
    To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of pharmacodynamic biomarker changes

  • Changes in the number of CTCs (Circulating Tumour Cells) [ Time Frame: From baseline until 21 days of combination therapy (Approx 6 assessments) ]
    To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of the total amount of circulating tumour cells (CTCs)

  • Changes in the level of total ctDNA (Circulating tumour DNA) [ Time Frame: From baseline until 21 days of combination therapy (approximately 11 assessments) ]
    To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of the total amount of ct DNA

  • Measure maximum plasma concentration (Cmax) [ Time Frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints) ]
    Measurement of Cmax as part of pharmacokinetic assessment

  • Measure maximum plasma concentration at steady state (Css max) [ Time Frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints) ]
    Measurement of Css max as part of pharmacokinetic assessment

  • Measure time to maximum concentration (tmax) [ Time Frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints) ]
    Measurement of tmax as part of pharmacokinetic assessment

  • Measure time to maximum concentration at steady state (tss max) [ Time Frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints) ]
    Measurement of tss max as part of pharmacokinetic assessments

  • Measurement of exposure by AUC (Area Under the Curve) calculation [ Time Frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints) ]
    Measurement of AUC as part of pharmacokinetic assessment

  • Measure minimum concentration at steady state (Css min) [ Time Frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints) ]
    Measurement of Css min as part of pharmacokinetic assessment

  • Measure rate of renal clearance (CLR) [ Time Frame: From Baseline until 7 days into treatment period ]
    Measurement of renal clearance (CLR) as part of pharmacokinetic assessment

  • Measure drug accumulation in the body (RAC) [ Time Frame: From Baseline until 31 days into combination treatment (maximum of 52 timepoints) ]
    Measurement of RAC as part of pharmacokinetic assessments


Estimated Enrollment: 225
Study Start Date: November 2015
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Safety and Tolerability
All patients will receive AZD0156 as a monotherapy or in combination with either olaparib, cytotoxic chemotherapies, or novel anti-cancer agents to assess safety and tolerability
Drug: AZD0156
All patients will receive AZD0156 as a monotherapy or in combination to assess safety and tolerability.
Drug: Olaparib
Module 1 combination with olaparib
Other Name: AZD2281

Detailed Description:

The study will consist of a number of study modules, each evaluating the safety and tolerability of AZD0156 with a specific combination agent. The combination option may require an initial monotherapy dose escalation to gain an understanding of pharmacokinetics, safety and tolerability before initiating dose escalation in combination. An oral formulation of AZD0156 will be used.

Module 1 explores AZD0156 in combination with olaparib Additional modules may be added to explore AZD0156 as a monotherapy or in combination with other agents and may be in different tumour types.

An expansion cohort in module 1 may enroll additional patients including, but not limited to, patients with advanced gastric adenocarcinoma, to explore further the safety, tolerability, pharmacokinetics and biological activity at selected dose(s) or alternate dosing schedules, and to get a preliminary assessment of efficacy .

During the dose expansion phase of any study module, a preliminary investigation of the effect of food on exposure may be made.

  Eligibility

Ages Eligible for Study:   18 Years to 130 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria for all parts of the study

  • Confirmation of locally advanced/metastatic cancer. Refractory or resistant to standard therapy, or have no effective standard
  • Aged at least 18 yrs
  • Reasonable health (performance status 0 or 1), stable over the previous 2 weeks
  • Females who can have children must use contraception; have a negative pregnancy test, & not be breast feeding
  • Sexually active male patients must use contraception for duration of study and for 3 months afterwards Inclusion criteria for Part B only
  • Tumour(s) that can be measured by CT or MRI, at least 1cm in size Inclusion for Module 1; olaparib specific part B
  • Confirmation of metastatic/locally advanced cancer type which failed to respond to standard treatments Exclusion criteria for all parts of the study
  • Prior treatment with an ATM inhibitor
  • Past medical history of an inflammatory type(interstitial) lung disease or current inflammatory lung disease
  • Radiotherapy within the last 4 weeks, except palliative radiotherapy for bone pain relief
  • Prior treatment with drugs that may cause lung damage
  • Poor of lung function
  • History/presence of muscle weakness or abnormal blood tests relating to muscle function
  • Cancer affecting the spinal cord and/or brain unless asymptomatic and stable
  • Any evidence of severe or uncontrolled diseases, active bleeding,kidney transplant, or active infection including liver infections (hepatitis B, hepatitis C) and human immunodeficiency virus (HIV).
  • Evidence of severe lung infections
  • Receiving, or having received during the four weeks prior to starting study treatment other chemotherapy treatment for your cancer
  • Treatment with certain doses of steroids during the two weeks prior to starting study treatment
  • A known sensitivity to AZD0156 or any of its components
  • Treatment with any unapproved medicine within 28 days prior to starting study treatment
  • Receiving, or having received medications, herbal supplements and/or foods that significantly affect how your liver works
  • Low numbers of certain blood cells
  • If your liver and kidney aren't working normally
  • If your heart isn't working normally or you have a strong family history of certain heart diseases
  • Other cancers within the past 3 years, except for certain types of cervical and skin cancers
  • Sickness and vomiting, digestive diseases or previous significant bowel removal
  • Patients with uncontrolled fitting
  • Infections requiring treatment
  • Other severe and/or uncontrolled medical conditions in addition to your cancer Exclusion for Module 1; olaparib specific part B
  • A blockage in your digestive system or severe bleeding from the stomach within 4 weeks before your take medication on the stuy
  • Patients with acute leukaemia or certain bone marrow diseases
  • Patients with a known sensitivity to olaparib or its components
  • Any previous treatment with drugs that work like olaparib.
  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: NCT02588105

Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
United States, Colorado
Research Site Not yet recruiting
Aurora, Colorado, United States
United States, New York
Research Site Recruiting
New York, New York, United States
Korea, Republic of
Research Site Recruiting
Seoul, Korea, Republic of
Spain
Research Site Recruiting
Barcelona, Spain
United Kingdom
Research Site Recruiting
Manchester, United Kingdom
Sponsors and Collaborators
AstraZeneca
INC Research
Investigators
Principal Investigator: Emma Dean, BMedSci, BM, BS, PhD, MRCP The Christie Hospital, Manchester, UK
  More Information

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02588105     History of Changes
Other Study ID Numbers: D6500C00001  2015-002572-25 
Study First Received: October 19, 2015
Last Updated: January 19, 2017

Keywords provided by AstraZeneca:
Phase I, open label study; safety and efficacy of AZD0156; ATM inhibitor

Additional relevant MeSH terms:
Olaparib
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 20, 2017