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Advanced Solid TumoursPhase 1AToMNCT02588105

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

A Phase 1 study testing AZD0156, Olaparib and irinotecan in people with Advanced Solid Tumours, run by AstraZeneca at 5 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 130 years
Conditions the study is for
Advanced Solid Tumours
What is being tested?
AZD0156, Olaparib and irinotecan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
84 participants
Where
5 sitesin 4 countries
Study dates
10 Nov 2015to 26 Jul 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 130 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 33Show fewer
  • 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)

Who cannot join

None listed.

Trial locations and contacts

5 sites in 4 countries.

5 sites in 4 countries

United States2 sites

  • Research Site

    Aurora, Colorado, 80045

  • Research Site

    New York, New York, 10033

Other trials in United States

South Korea1 site

  • Research Site

    Seoul, 03080

Other trials in South Korea

Spain1 site

  • Research Site

    Barcelona, 08035

Other trials in Spain

United Kingdom1 site

  • Research Site

    Manchester, M20 4BX

Other trials in United Kingdom

About this study

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

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.

Read the 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

Being tested
AZD0156, Olaparib, irinotecan, Fluorouracil, Folinic Acid
Keywords
Phase I, open label study; safety and efficacy of AZD0156; ATM inhibitor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD0156Drug

    All patients will receive AZD0156 as a monotherapy or in combination to assess safety and tolerability.

  • OlaparibDrug

    Also called AZD2281, Lynparza

    Module 1 combination with olaparib

  • irinotecanDrug

    Also called Camptosar

    Module 2 combination with irinotecan/FOLFIRI

  • FluorouracilDrug

    Also called 5-FU, Adrucil

    Module 2 combination with irinotecan/FOLFIRI

  • Folinic AcidDrug

    Also called leucovorin

    Module 2 combination with irinotecan/FOLFIRI

Study groups in NCT02588105
Study groupRoleWhat they receive
Safety and TolerabilityExperimentalAll 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
Receives: Drug: AZD0156; Drug: Olaparib; Drug: irinotecan; Drug: Fluorouracil; Drug: Folinic Acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability - Number of patients experiencing adverse events

    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

    Measured: Informed consent until end of Safety Follow-up (approximately 6 months)

Secondary outcomes (14)

  1. Anti-tumour activity assessed through tumour measurements

    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

    Measured: Baseline and then every 6 weeks until Safety follow-up (approximately 6 months)

  2. Changes in expression levels of proteins that may be impacted by ATM protein activity or inhibition

    To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of pharmacodynamic biomarker changes

    Measured: From baseline until 21 days of combination therapy (Approximately 11 assessments)

  3. Changes in the number of CTCs (Circulating Tumour Cells)

    To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of the total amount of circulating tumour cells (CTCs)

    Measured: From baseline until 21 days of combination therapy (Approx 6 assessments)

  4. Changes in the level of total ctDNA (Circulating tumour DNA)

    To obtain a preliminary assessment of AZD0156 activity in the tumour by evaluation of the total amount of ct DNA

    Measured: From baseline until 21 days of combination therapy (approximately 11 assessments)

  5. Measure maximum plasma concentration (Cmax)

    Measurement of Cmax as part of pharmacokinetic assessment

    Measured: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)

  6. Measure maximum plasma concentration at steady state (Css max)

    Measurement of Css max as part of pharmacokinetic assessment

    Measured: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)

  7. Measure time to maximum concentration (tmax)

    Measurement of tmax as part of pharmacokinetic assessment

    Measured: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)

  8. Measure time to maximum concentration at steady state (tss max)

    Measurement of tss max as part of pharmacokinetic assessments

    Measured: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)

  9. Measurement of exposure by AUC (Area Under the Curve) calculation

    Measurement of AUC as part of pharmacokinetic assessment

    Measured: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)

  10. Measure minimum concentration at steady state (Css min)

    Measurement of Css min as part of pharmacokinetic assessment

    Measured: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)

  11. Measure rate of renal clearance (CLR)

    Measurement of renal clearance (CLR) as part of pharmacokinetic assessment

    Measured: From Baseline until 7 days into treatment period

  12. Measure drug accumulation in the body (RAC)

    Measurement of RAC as part of pharmacokinetic assessments

    Measured: From Baseline until 31 days into combination treatment (maximum of 52 timepoints)

  13. Identification of Maximum Tolerated Dose (MTD)

    Safety and tolerability of AZD0156 alone or in combination with cytotoxic chemotherapies or novel anti-cancer agents as assessed through collection of Adverse Events

    Measured: Informed consent untli end of Dose Limiting Toxicity (DLT) period - Approx 1 month

  14. Overall Survival (Part B Only)

    Period of time from the start of treatment until end of life from any cause

    Measured: From start of treatment until the end of Long Term Follow-up (Approx 12 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Oct 2015 (estimated)
  2. Study start10 Nov 2015
  3. Primary completion13 Sep 2019
  4. Study completion26 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02588105
Sponsor's protocol ID
D6500C00001
Other IDs
2015-002572-25, 2015
Acronym
AToM
Status last verified
Sep 2022
First submitted
19 Oct 2015
Last updated
19 Sep 2022
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Expanded access
Available

Publications

  • Smith G, Alholm Z, Coleman RL, Monk BJ. DNA Damage Repair Inhibitors-Combination Therapies. Cancer J. 2021 Nov-Dec 01;27(6):501-505. doi: 10.1097/PPO.0000000000000561.

    PubMed 34904813

  • Riches LC, Trinidad AG, Hughes G, Jones GN, Hughes AM, Thomason AG, Gavine P, Cui A, Ling S, Stott J, Clark R, Peel S, Gill P, Goodwin LM, Smith A, Pike KG, Barlaam B, Pass M, O'Connor MJ, Smith G, Cadogan EB. Pharmacology of the ATM Inhibitor AZD0156: Potentiation of Irradiation and Olaparib Responses Preclinically. Mol Cancer Ther. 2020 Jan;19(1):13-25. doi: 10.1158/1535-7163.MCT-18-1394. Epub 2019 Sep 18.

    PubMed 31534013

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AZD0156, Olaparib and irinotecan in people with Advanced Solid Tumours, run by AstraZeneca at 5 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, South Korea, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability - Number of patients experiencing adverse events (time frame: Informed consent until end of Safety Follow-up (approximately 6 months)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02588105, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2022.

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