A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC
NCT ID: NCT04550104
Last Updated: 2025-12-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1
200 participants
INTERVENTIONAL
2021-03-17
2028-03-31
Brief Summary
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Detailed Description
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The study will use new drugs that affect how cells repair DNA damage, called DNA damage response inhibitors (DDRi). These will be given together with radiotherapy to hopefully improve the effectiveness of radiotherapy, followed by up to 12 months of durvalumab immunotherapy in selected study arms to develop the trial in line with the standard of care for NSCLC. The study will try to find out the most effective and safe dose of this combination treatment. This will be a clinical trial where patients due to have radiotherapy, with the hope of successful treatment that could lead to cure from their cancer or extension of life, will be offered entry onto the study. All patients will receive their radiotherapy, with 3 out of every 4 people also receiving a single DDRi drug alongside this. Both patients and study doctors will know prior to the start of the actual treatment whether a DDRi will be given, and if so which one; no placebos will be used. The patients will be followed closely to check for side effects and to assess how their cancer is responding to treatment. Blood samples will be taken to monitor treatment progress and to try to predict which patients are most likely to benefit from this type of combined treatment.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Radiotherapy only
Radiotherapy
Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.
Olaparib + radiotherapy
Radiotherapy
Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.
Olaparib Oral Tablet [Lynparza]
Oral tablet
AZD1390 + radiotherapy
Radiotherapy
Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.
AZD1390
Oral tablet
Ceralasertib (AZD6738) + radiotherapy + Consolidation durvalumab
This study arm will include up to 12 months of consolidation durvalumab for eligible participants following the completion of radiotherapy +/- DDRi.
Radiotherapy
Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.
Ceralasertib
Oral Tablet
Durvalumab
1500mg iv infusion
AZD5305 + radiotherapy + Consolidation durvalumab
This study arm will include up to 12 months of consolidation durvalumab for eligible participants following the completion of radiotherapy +/- DDRi.
Radiotherapy
Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.
AZD5305
Oral Tablet
Durvalumab
1500mg iv infusion
RT + consolidation durvalumab
Radiotherapy
Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.
Durvalumab
1500mg iv infusion
Arm D - did not proceed
Arm D - did not proceed
Radiotherapy
Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.
Interventions
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Radiotherapy
Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.
Olaparib Oral Tablet [Lynparza]
Oral tablet
AZD1390
Oral tablet
Ceralasertib
Oral Tablet
AZD5305
Oral Tablet
Durvalumab
1500mg iv infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Not suitable for concurrent chemoradiotherapy/surgery due to tumour or patient factors
3. Stage IIB and III (TNM 8th Edition).
4. Planned to receive RT at curative intent doses (i.e., 60Gy) as part of treatment plan (either with or without induction chemotherapy).
5. Patient considered suitable for radical RT by the local lung cancer multidisciplinary team and a clinical oncologist.
6. If chemotherapy has been given previously, the maximum interval between the last day of chemotherapy and the start of RT \<10 weeks.
7. Age ≥18
8. Life expectancy estimated to be greater than 6 months.
9. Karnofsky Performance status ≥70.
10. MRC dyspnoea score \<3.
11. Forced expiratory volume in one second (FEV1) ≥35% predicted and diffusing capacity of the lungs for carbon monoxide (DLCO or TLCO) ≥35% predicted.
12. Patient must be fully informed about the study and have signed the informed consent form.
13. Patient must be willing and able to comply with the protocol, have mental capacity and (if relevant) use effective contraception throughout treatment and for 4 months for women of childbearing potential, and 6 months for men after treatment completion. Treatment is defined as including the last dose of durvalumab or DDRi in the consolidation phase.
14. Adequate organ function as defined in master protocol.
15. Patient has a body weight of \>30kg.
1. A minimum of 4 and a maximum of 8 weeks\* have elapsed following completion of RT
2. Any toxicities from RT have resolved to grade 1. If patient has pneumonitis following RT treatment, this must be asymptomatic (grade 1). If pneumonitis is ≥2 or requiring steroids, then participant is not eligible
3. Karnofsky Performance status ≥70
4. The laboratory requirements set out in Table 1 of the master protocol are met
5. Patient has no known hypersensitivity to the excipients of durvalumab
6. Patient has body weight of \>30kg \*Investigators should ideally aim to start consolidation treatment within 6 weeks, following the receipt of the CT scan results to rule out progression.
Exclusion Criteria
2. Confirmed progressive disease during induction chemotherapy.
3. Participation in a study of an investigational agent or using an investigational device within 4 weeks prior to the anticipated start of treatment.
4. Current or previous malignant disease which may impact on a patient's estimated life expectancy (other than NSCLC).
5. History of interstitial pneumonitis.
6. Prior thoracic radiotherapy.
7. Prior treatment with pneumotoxic drugs, e.g. busulfan, bleomycin, within the past year. If prior therapy in lifetime, then exclude if history of pulmonary toxicities from administration. Patients who have received treatment with nitrosoureas (e.g., carmustine, lomustine) in the year before study entry without experiencing lung toxicity are allowed on study.
8. Mean resting corrected QT interval (QTcF) \>470 msec obtained from 3 electrocardiograms.
9. Received a prior autologous or allogeneic organ or tissue transplantation.
10. Patients unable to swallow orally administered medications or chronic gastrointestinal (GI) disease likely to interfere with absorption of IMP in the opinion of the treating investigator (e.g. malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease etc.).
11. Grade 2 or higher peripheral sensory neuropathy.
12. Known positive test for human immunodeficiency virus, active hepatitis B or C infection.
13. Positive pregnancy test (at eligibility assessment for women of childbearing potential) or breast-feeding women.
14. Patients with persistent toxicities (\>CTCAE grade 2) caused by previous cancer therapy, excluding alopecia.
15. Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
16. Major surgery within 2 weeks of confirmation of eligibility.
17. Patients considered a poor medical risk by the investigator due to a serious, uncontrolled medical disorder, non-malignant system disease or active uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, uncontrolled hypertension, uncontrolled atrial fibrillation, active bleeding, recent (within 3 months) myocardial infarction, major seizure, active COVID-19, any psychiatric disorder that prohibits obtaining informed consent.
18. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.
1. Progressive disease during RT or at the end of RT treatment response assessment.
2. Participant declines treatment in the consolidation phase.
3. Patients who have received prior anti-PD-1 or anti PD-L1 treatment.
4. Major surgery within 4 weeks of confirmation of eligibility for consolidation phase.
5. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
6. Patients considered a poor medical risk by the investigator due to a serious, uncontrolled medical disorder, non-malignant system disease, active GI infection or active uncontrolled infection.
7. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease e.g., colitis or Crohn's disease), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc).
18 Years
ALL
No
Sponsors
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University of Manchester
OTHER
Newcastle University
OTHER
University of Oxford
OTHER
The Leeds Teaching Hospitals NHS Trust
OTHER
Beatson West of Scotland Cancer Centre
UNKNOWN
University of Glasgow
OTHER
Velindre NHS Trust
OTHER_GOV
University College London Hospitals
OTHER
Queen's University, Belfast
OTHER
University of Sheffield
OTHER
University of Leeds
OTHER
Responsible Party
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Principal Investigators
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Alastair Greystoke, MB ChB, MSc, PhD
Role: PRINCIPAL_INVESTIGATOR
Newcastle University
Corinne Faivre-Finn, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of Manchester
Locations
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Belfast City Hospital
Belfast, , United Kingdom
Birmingham Heartlands Hospital
Birmingham, , United Kingdom
Addenbrooke's Hospital
Cambridge, , United Kingdom
Velindre Cancer Centre
Cardiff, , United Kingdom
The Royal Marsden Hospital Chelsea
Chelsea, , United Kingdom
Western General Hospital
Edinburgh, , United Kingdom
St James's University Hospital
Leeds, , United Kingdom
The Clatterbridge Cancer Centre
Liverpool, , United Kingdom
St Bartholomew's Hospitals
London, , United Kingdom
University College Hospital London
London, , United Kingdom
The Christie NHS Foundation Trust
Manchester, , United Kingdom
Freeman Hospital, Newcastle upon Tyne Hospitals NHS Trust
Newcastle upon Tyne, , United Kingdom
Weston Park Hospital
Sheffield, , United Kingdom
The Royal Marsden Sutton
Sutton, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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Role: primary
CTRU CONCORDE
Role: primary
Role: primary
Role: primary
Role: primary
Role: primary
Role: primary
CTRU CONCORDE
Role: primary
CTRU CONCORDE
Role: primary
Role: primary
Role: primary
Alastair Greystoke
Role: primary
Role: primary
Role: primary
References
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Faivre-Finn C, Brown S, Ryan A, Greystoke A; CONCORDE Investigators. The UK at the Forefront of Innovative Drug-Radiotherapy Combination Clinical Trials: Introducing the CONCORDE Platform. Clin Oncol (R Coll Radiol). 2020 Jun;32(6):358-362. doi: 10.1016/j.clon.2020.02.003. Epub 2020 Feb 24. No abstract available.
Walls GM, Oughton JB, Chalmers AJ, Brown S, Collinson F, Forster MD, Franks KN, Gilbert A, Hanna GG, Hannaway N, Harrow S, Haswell T, Hiley CT, Hinsley S, Krebs M, Murden G, Phillip R, Ryan AJ, Salem A, Sebag-Montefoire D, Shaw P, Twelves CJ, Walker K, Young RJ, Faivre-Finn C, Greystoke A. CONCORDE: A phase I platform study of novel agents in combination with conventional radiotherapy in non-small-cell lung cancer. Clin Transl Radiat Oncol. 2020 Sep 22;25:61-66. doi: 10.1016/j.ctro.2020.09.006. eCollection 2020 Nov.
Walker K, Hinsley S, Phillip R, Oughton JB, Murden G, Chalmers AJ, Faivre-Finn C, Greystoke A, Brown SR; CONCORDE Investigators. Implementation of the Time-to-Event Continuous Reassessment Method Design in a Phase I Platform Trial Testing Novel Radiotherapy-Drug Combinations-CONCORDE. JCO Precis Oncol. 2022 Nov;6:e2200133. doi: 10.1200/PO.22.00133.
Other Identifiers
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2020-000206-28
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
282001
Identifier Type: OTHER
Identifier Source: secondary_id
A28890
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
MO20/118073
Identifier Type: -
Identifier Source: org_study_id