Solid Tumour Refractory to Conventional TreatmentPhase 1PatriotNCT02223923
Phase I Study to Assess Safety of AZD6738 Alone and in Combination With Radiotherapy in Patients With Solid Tumours
A Phase 1 study testing AZD6738 and Palliative radiotherapy in people with Solid Tumour Refractory to Conventional Treatment, run by Royal Marsden NHS Foundation Trust at 3 sites in United Kingdom.
Trial summary
This study will investigate the use of a new drug targeting the DNA repair pathway AZD6738, an ATR inhibitor). Many tumours have lost important DNA repair functions and rely more heavily on a few remaining repair pathways to survive. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumour Refractory to Conventional Treatment
- What is being tested?
- AZD6738 and Palliative radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 87 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Jul 2014to 30 Dec 2025
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically documented solid tumour refractory to conventional treatment
- Evidence of measurable or evaluable disease by RECIST 1.1
- Age must be 18 years or over.
- ECOG performance status 0-1 (part A); 0-2 (parts B and C)
- Life expectancy of at least 3 months.
- Patients must have normal organ and bone marrow function measured within 7 days prior to administration of study treatment as defined below:
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- Signed informed consent indicating that the subject is aware of the neoplastic nature of their disease and have been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
- Willing and able to comply with scheduled visits, tissue sampling, treatment plan, and laboratory tests.
- Able to swallow, absorb and retain oral medication.
Who cannot join
- Therapy with any other investigational medical product (IMP) concurrently or within 28 days prior to signing of consent.
- Pregnant or breast-feeding women.
- Ability to become pregnant (or already pregnant or lactating).
- Clinically significant cardiac disease including:
- Known HIV positive or active hepatitis B or C infection
- Uncontrolled active infection
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- Symptomatic and progressive or steroid-requiring brain metastases or leptomeningeal disease involvement.
- Uncontrolled hypertension requiring clinical intervention, hypertension requiring 2 or more antihypertensive agents
- Dementia or altered mental status that would prohibit informed consent.
- Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal Investigator, would make the subject inappropriate for this study.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites
University College Hospital
London, NW1 2BU
Guys and St Thomas' NHS Foundation Trust
London, SE1 9RT
Royal Marsden Hospital
London, SW3 6JJ
About this study
Official title: A Phase I Study to Assess the Tolerability, Safety and Biological Effects of ATR Inhibitor (AZD6738) as a Single Agent and in Combination With Palliative Radiation Therapy in Patients With Solid Tumours
This study will investigate the use of a new drug targeting the DNA repair pathway AZD6738, an ATR inhibitor). Many tumours have lost important DNA repair functions and rely more heavily on a few remaining repair pathways to survive. Preclinical studies indicate that, in these tumours, preventing the function of the remaining pathways will lead to tumour cell death, while sparing normal cells. This study aims to investigate the safety and tolerability of the new drug in patients with advanced cancer, as well as in combination with palliative radiotherapy, where the drug may increase the effectiveness of radiotherapy by preventing repair of the radiationinduced DNA damage. As the drug has only been given to a small number of patients, the study will focus on safety and finding the correct dose to proceed to further studies, although preliminary signs of drug activity will also be examined.
The initial part of the study will administer increasing doses of the drug to groups of patients with advanced cancer who have no standard anticancer treatment options available. Testing will establish whether the drug levels in the body and tumour are adequate for the drug to have an effect, and any toxicity will be assessed. After the recommended dose is established, the recommended dose schedule will be stablished by trialing different schedules. Participants will be tested to see if their tumours lack the main DNA repair pathway (those who are predicted to have a better response to this drug). Finally, the drug will be given to patients with advanced cancer who require a course of radiotherapy for symptom control - the drug will be tested at different doses and with different doses of radiotherapy.
Side effects will be monitored and tests will establish whether the drug is enhancing the radiotherapy effect in the tumours or normal tissues.
- Being tested
- AZD6738, Palliative radiotherapy
- Keywords
- Phase 1, Maximimum tolerated dose, ATR Inhibitor, Radiotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD6738Drug
Palliative radiotherapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation | Experimental | AZD6738 PO 20 to 380mg BD increasing Receives: Drug: AZD6738 |
| AZD6738 - Expansion Phase | Experimental | AZD6738 starting dose and regimen to be determined in dose escalation phase Receives: Drug: AZD6738 |
| AZD6738 + Radiotherapy (Head and Neck) | Experimental | AZD6738 starting dose to be determined in dose escalation phase + increasing doses of radiotherapy (20 or 30Gy) Receives: Drug: AZD6738; Radiation: Palliative radiotherapy |
| AZD6738 + Radiotherapy (Abdomen / Pelvis) | Experimental | AZD6738 starting dose to be determined in dose escalation phase + increasing doses of radiotherapy (20 or 30Gy) Receives: Drug: AZD6738; Radiation: Palliative radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identifying the maximum tolerated dose (MTD) of AZD6738 as a single-agent; and in combination with palliative radiation schedules.
Measured: 4 weeks
Secondary outcomes (3)
Determining causality of each adverse event in relation to AZD6738 and grading severity according to CTCAE version 4;
Measured: 4 weeks
Single and multiple dose pharmacokinetics: measurement of plasma levels of AZD6738 at pre-defined intervals in the dose-escalation part of the study in order to establish pharmacokinetic parameters;
Measured: Day 0 and Day 1
Any response (stable disease, partial response or complete response) in any of the patients by physical, tumour marker and/or radiographic assessments of tumours as determined by RECIST 1.1.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2014 (estimated)
- Study startJul 2014
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumour Refractory to Conventional TreatmentStudies of the same condition, open and under way.
- More trials run by Royal Marsden NHS Foundation TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 87 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Marsden NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Cancer Research UK, RM/ICR Biomedical Research Centre
- Responsible party
- Sponsor
- Investigators
- Kevin Harrington, MBBS MRCP FRCR, Principal investigator, Institute of Cancer Research, United KingdomMartin Forster, Principal investigator, University College London Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02223923
- Sponsor's protocol ID
- CCR4087
- Acronym
- Patriot
- Status last verified
- Oct 2023
- First submitted
- 21 Aug 2014
- Last updated
- 1 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Dillon MT, Guevara J, Mohammed K, Patin EC, Smith SA, Dean E, Jones GN, Willis SE, Petrone M, Silva C, Thway K, Bunce C, Roxanis I, Nenclares P, Wilkins A, McLaughlin M, Jayme-Laiche A, Benafif S, Nintos G, Kwatra V, Grove L, Mansfield D, Proszek P, Martin P, Moore L, Swales KE, Banerji U, Saunders MP, Spicer J, Forster MD, Harrington KJ. Durable responses to ATR inhibition with ceralasertib in tumors with genomic defects and high inflammation. J Clin Invest. 2024 Jan 16;134(2):e175369. doi: 10.1172/JCI175369.
PubMed 37934611
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Assess the Tolerability, Safety and Biological Effects of ATR Inhibitor (AZD6738) as a Single Agent and in Combination With Palliative Radiation Therapy in Patients With Solid Tumours
- ClinicalTrials.gov ID
- NCT02223923
- Acronym / sponsor ID
- Patriot / CCR4087
- Keywords
- Phase 1, Maximimum tolerated dose, ATR Inhibitor, Radiotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 87 participants (estimated)
- Lead sponsor
- Royal Marsden NHS Foundation TrustUniversity, hospital or other
- Collaborators
- AstraZeneca, Cancer Research UK, RM/ICR Biomedical Research Centre
- Study start
- Jul 2014 (actual)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 22 Aug 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate the use of a new drug targeting the DNA repair pathway AZD6738, an ATR inhibitor). Many tumours have lost important DNA repair functions and rely more heavily on a few remaining repair pathways to survive. Preclinical studies indicate that, in these tumours, preventing the function of the remaining pathways will lead to tumour cell death, while sparing normal cells. This study aims to investigate the safety and tolerability of the new drug in patients with advanced cancer, as well as in combination with palliative radiotherapy, where the drug may increase the effectiveness of radiotherapy by preventing repair of the radiationinduced DNA damage. As the drug has only been given to a small number of patients, the study will focus on safety and finding the correct dose to proceed to further studies, although preliminary signs of drug activity will also be examined.
The initial part of the study will administer increasing doses of the drug to groups of patients with advanced cancer who have no standard anticancer treatment options available. Testing will establish whether the drug levels in the body and tumour are adequate for the drug to have an effect, and any toxicity will be assessed. After the recommended dose is established, the recommended dose schedule will be stablished by trialing different schedules. Participants will be tested to see if their tumours lack the main DNA repair pathway (those who are predicted to have a better response to this drug). Finally, the drug will be given to patients with advanced cancer who require a course of radiotherapy for symptom control - the drug will be tested at different doses and with different doses of radiotherapy.
Side effects will be monitored and tests will establish whether the drug is enhancing the radiotherapy effect in the tumours or normal tissues.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation | Experimental | Drug: AZD6738AZD6738 PO 20 to 380mg BD increasing |
| AZD6738 - Expansion Phase | Experimental | Drug: AZD6738AZD6738 starting dose and regimen to be determined in dose escalation phase |
| AZD6738 + Radiotherapy (Head and Neck) | Experimental | Drug: AZD6738, Radiation: Palliative radiotherapyAZD6738 starting dose to be determined in dose escalation phase + increasing doses of radiotherapy (20 or 30Gy) |
| AZD6738 + Radiotherapy (Abdomen / Pelvis) | Experimental | Drug: AZD6738, Radiation: Palliative radiotherapyAZD6738 starting dose to be determined in dose escalation phase + increasing doses of radiotherapy (20 or 30Gy) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically or cytologically documented solid tumour refractory to conventional treatment
- Evidence of measurable or evaluable disease by RECIST 1.1
- Age must be 18 years or over.
- ECOG performance status 0-1 (part A); 0-2 (parts B and C)
- Life expectancy of at least 3 months.
Key exclusion criteria (10 listed)
- Therapy with any other investigational medical product (IMP) concurrently or within 28 days prior to signing of consent.
- Pregnant or breast-feeding women.
- Ability to become pregnant (or already pregnant or lactating).
- Clinically significant cardiac disease including:
- Known HIV positive or active hepatitis B or C infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD6738 | Drug | AZD6738 + Radiotherapy (Abdomen / Pelvis), AZD6738 + Radiotherapy (Head and Neck), AZD6738 - Expansion Phase, Dose Escalation |
| Palliative radiotherapy | Radiation | AZD6738 + Radiotherapy (Abdomen / Pelvis), AZD6738 + Radiotherapy (Head and Neck) |
Primary outcome
Identifying the maximum tolerated dose (MTD) of AZD6738 as a single-agent; and in combination with palliative radiation schedules.
Time frame: 4 weeks
3 secondary outcomes
Determining causality of each adverse event in relation to AZD6738 and grading severity according to CTCAE version 4;
Time frame: 4 weeks
Single and multiple dose pharmacokinetics: measurement of plasma levels of AZD6738 at pre-defined intervals in the dose-escalation part of the study in order to establish pharmacokinetic parameters;
Time frame: Day 0 and Day 1
Any response (stable disease, partial response or complete response) in any of the patients by physical, tumour marker and/or radiographic assessments of tumours as determined by RECIST 1.1.
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
- Derived from this study: PubMed 37934611Dillon MT, Guevara J, Mohammed K, Patin EC, Smith SA, Dean E, Jones GN, Willis SE, Petrone M, Silva C, Thway K, Bunce C, Roxanis I, Nenclares P, Wilkins A, McLaughlin M, Jayme-Laiche A, Benafif S, Nintos G, Kwatra V, Grove L, Mansfield D, Proszek P, Martin P, Moore L, Swales KE, Banerji U, Saunders MP, Spicer J, Forster MD, Harrington KJ. Durable responses to ATR inhibition with ceralasertib in tumors with genomic defects and high inflammation. J Clin Invest. 2024 Jan 16;134(2):e175369. doi: 10.1172/JCI175369.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Harrington, MBBS MRCP FRCR principal investigator
Institute of Cancer Research, United Kingdom
Martin Forster principal investigator
University College London Hospitals
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD6738 and Palliative radiotherapy in people with Solid Tumour Refractory to Conventional Treatment, run by Royal Marsden NHS Foundation Trust at 3 sites in United Kingdom.
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 9 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 1 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in 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?
Results are not available in the source record.
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?
Identifying the maximum tolerated dose (MTD) of AZD6738 as a single-agent; and in combination with palliative radiation schedules. (time frame: 4 weeks). 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 NCT02223923, which also lists 1 linked publication.
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 1 Aug 2025.