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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)

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ClinicalTrials.gov Identifier: NCT02588105
Recruitment Status : Recruiting
First Posted : October 27, 2015
Last Update Posted : December 3, 2018
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
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 or disease Intervention/treatment Phase
Advanced Solid Tumours Drug: AZD0156 Drug: Olaparib Drug: irinotecan Drug: Fluorouracil Drug: Folinic Acid Phase 1

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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 Module 2 explores AZD0156 in combination with irinotecan/FOLFIRI Additional modules may be added to explore AZD0156 as a monotherapy or in combination with other agents and may be in different tumour types.

Expansion cohorts may enroll additional patients 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 .

Module 1 includes an expansion cohort in locally advanced/metastatic tumours including but not limited to gastric adenocarcinoma Module 2 includes an expansion cohort in colorectal cancer


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
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
Actual Study Start Date : November 10, 2015
Estimated Primary Completion Date : August 30, 2019
Estimated Study Completion Date : August 30, 2019

Arm Intervention/treatment
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, Lynparza

Drug: irinotecan
Module 2 combination with irinotecan/FOLFIRI
Other Name: Camptosar

Drug: Fluorouracil
Module 2 combination with irinotecan/FOLFIRI
Other Name: 5-FU, Adrucil

Drug: Folinic Acid
Module 2 combination with irinotecan/FOLFIRI
Other Name: leucovorin




Primary Outcome Measures :
  1. 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 :
  1. 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

  2. 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

  3. 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)

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. Identification of Maximum Tolerated Dose (MTD) [ Time Frame: Informed consent untli end of Dose Limiting Toxicity (DLT) period - Approx 1 month ]
    Safety and tolerability of AZD0156 alone or in combination with cytotoxic chemotherapies or novel anti-cancer agents as assessed through collection of Adverse Events

  14. Overall Survival (Part B Only) [ Time Frame: From start of treatment until the end of Long Term Follow-up (Approx 12 months) ]
    Period of time from the start of treatment until end of life from any cause



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
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 Part B
  • Confirmation of metastatic/locally advanced cancer of specific tumour 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
  • 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 (Module 1), or components of FOLFIRI (Module 2)
  • Any previous treatment with drugs that work like olaparib. (Module 1 Only)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02588105


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

Locations
United States, Colorado
Research Site Recruiting
Aurora, Colorado, United States, 80045
United States, New York
Research Site Recruiting
New York, New York, United States, 10033
Korea, Republic of
Research Site Recruiting
Seoul, Korea, Republic of, 03080
Spain
Research Site Recruiting
Barcelona, Spain, 08035
United Kingdom
Research Site Recruiting
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
AstraZeneca
Syneos Health
Investigators
Principal Investigator: Matthew Krebs, BMedSci, BM, BS, PhD, MRCP The Christie Hospital, Manchester, UK

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02588105     History of Changes
Other Study ID Numbers: D6500C00001
2015-002572-25 ( EudraCT Number )
First Posted: October 27, 2015    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018

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

Additional relevant MeSH terms:
Irinotecan
Olaparib
Fluorouracil
Antineoplastic Agents
Leucovorin
Levoleucovorin
Folic Acid
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Poly(ADP-ribose) Polymerase Inhibitors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Hematinics