A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC
CONCORDE
A Platform Study of DNA Damage Response Inhibitors in Combination With Conventional Radiotherapy in Non Small Cell Lung Cancer
4 other identifiers
interventional
200
1 country
14
Brief Summary
CONCORDE is a multi-institution, multi-arm, Phase IB study that will determine the recommended phase II dose (RP2D) and safety profiles of different DNA damage repair inhibitors (DDRis) when given in an open label fashion in combination with fixed dose curative intent radiotherapy (RT) in patients with stage IIB/IIIA/IIIB NSCLC, followed by up to 12 months of consolidation durvalumab immunotherapy in selected study arms. The RP2D will be evaluated by incorporating the number of observed dose limiting toxicities (DLTs) into a time to event continuous reassessment method (TiTE- CRM) model within each of the experimental arms. TiTE-CRM is used here to take into account longer-term toxicities up to 13.5 months post start of radiotherapy and use these to inform dose escalation decision making.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2021
Longer than P75 for phase_1
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 24, 2020
CompletedFirst Posted
Study publicly available on registry
September 16, 2020
CompletedStudy Start
First participant enrolled
March 17, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2028
ExpectedDecember 19, 2025
March 1, 2025
5 years
June 24, 2020
December 18, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Dose limiting Toxicities
Dose-limiting toxicities (DLTs), within 13.5 months of starting radiotherapy, in order to establish the Recommended Phase II Dose (RP2D) of each DDRi-RT combination.
13.5 months after start of radiotherapy
Secondary Outcomes (9)
Safety and toxicity
2 years after end of RT
Treatment compliance
End of trial treatment (DDRi and RT)
Best overall response
2 years after end of RT
Disease control
2 years after end of RT
Progression-free survival
2 years post-RT
- +4 more secondary outcomes
Other Outcomes (6)
Assessment of mutations in components of DDR pathway in archival tumour and cfDNA prior to therapy
2 years after end of RT
Assessment of T cells within the archival tumour specimens
2 years after end of RT
Changes in cfDNA during and following treatment with DDRi-RT compared to RT alone.
2 years after end of RT
- +3 more other outcomes
Study Arms (7)
Radiotherapy only
ACTIVE COMPARATOROlaparib + radiotherapy
EXPERIMENTALAZD1390 + radiotherapy
EXPERIMENTALCeralasertib (AZD6738) + radiotherapy + Consolidation durvalumab
EXPERIMENTALThis study arm will include up to 12 months of consolidation durvalumab for eligible participants following the completion of radiotherapy +/- DDRi.
AZD5305 + radiotherapy + Consolidation durvalumab
EXPERIMENTALThis study arm will include up to 12 months of consolidation durvalumab for eligible participants following the completion of radiotherapy +/- DDRi.
RT + consolidation durvalumab
ACTIVE COMPARATORArm D - did not proceed
EXPERIMENTALArm D - did not proceed
Interventions
Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.
Oral Tablet
1500mg iv infusion
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed NSCLC (patients where the local MDT agree the diagnosis is NSCLC after review of the available pathology and imaging at MDT can be enrolled after discussion with the CI).
- Not suitable for concurrent chemoradiotherapy/surgery due to tumour or patient factors
- Stage IIB and III (TNM 8th Edition).
- Planned to receive RT at curative intent doses (i.e., 60Gy) as part of treatment plan (either with or without induction chemotherapy).
- Patient considered suitable for radical RT by the local lung cancer multidisciplinary team and a clinical oncologist.
- If chemotherapy has been given previously, the maximum interval between the last day of chemotherapy and the start of RT \<10 weeks.
- Age ≥18
- Life expectancy estimated to be greater than 6 months.
- Karnofsky Performance status ≥70.
- MRC dyspnoea score \<3.
- Forced expiratory volume in one second (FEV1) ≥35% predicted and diffusing capacity of the lungs for carbon monoxide (DLCO or TLCO) ≥35% predicted.
- Patient must be fully informed about the study and have signed the informed consent form.
- 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.
- Adequate organ function as defined in master protocol.
- Patient has a body weight of \>30kg.
You may not qualify if:
- Mixed non-small cell and small cell tumours.
- Confirmed progressive disease during induction chemotherapy.
- Participation in a study of an investigational agent or using an investigational device within 4 weeks prior to the anticipated start of treatment.
- Current or previous malignant disease which may impact on a patient's estimated life expectancy (other than NSCLC).
- History of interstitial pneumonitis.
- Prior thoracic radiotherapy.
- 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.
- Mean resting corrected QT interval (QTcF) \>470 msec obtained from 3 electrocardiograms.
- Received a prior autologous or allogeneic organ or tissue transplantation.
- 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.).
- Grade 2 or higher peripheral sensory neuropathy.
- Known positive test for human immunodeficiency virus, active hepatitis B or C infection.
- Positive pregnancy test (at eligibility assessment for women of childbearing potential) or breast-feeding women.
- Patients with persistent toxicities (\>CTCAE grade 2) caused by previous cancer therapy, excluding alopecia.
- Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML.
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- The Leeds Teaching Hospitals NHS Trustcollaborator
- Beatson West of Scotland Cancer Centrecollaborator
- University of Glasgowcollaborator
- Velindre NHS Trustcollaborator
- University College London Hospitalscollaborator
- Queen's University, Belfastcollaborator
- University of Sheffieldcollaborator
- University of Leedslead
- University of Manchestercollaborator
- Newcastle Universitycollaborator
- University of Oxfordcollaborator
Study Sites (14)
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
Related Publications (3)
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.
PMID: 32107107BACKGROUNDWalls 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.
PMID: 33072895BACKGROUNDWalker 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.
PMID: 36446040DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alastair Greystoke, MB ChB, MSc, PhD
Newcastle University
- PRINCIPAL INVESTIGATOR
Corinne Faivre-Finn, MD, PhD
University of Manchester
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 24, 2020
First Posted
September 16, 2020
Study Start
March 17, 2021
Primary Completion
March 1, 2026
Study Completion (Estimated)
March 1, 2028
Last Updated
December 19, 2025
Record last verified: 2025-03
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- At the end of the trial, i.e. usually when all primary and secondary endpoints have been met and all key analyses are complete.
- Access Criteria
- Contact CTRU-DataAccess@leeds.ac.uk in the first instance. No individual participant data will be released before an appropriate agreement is in place setting out the conditions of release. The agreement will govern data retention, usually stipulating that data recipients must delete their copy of the released data at the end of the planned project. The CTRU encourages a collaborative approach to data sharing, and believe it is best practice for researchers who generated datasets to be involved in subsequent uses of those datasets. Recipients of trial data for secondary research will also receive data dictionaries, copies of key trial documents and any other information required to understand and reuse the released datasets. The conditions of release for aggregate data may differ from those applying to individual participant data. Requests for aggregate data should also be sent to the above email address to discuss and agree suitable requirements for release.
De-identified individual participant data datasets generated and/or analysed during the current study will be available upon request from the Clinical Trials Research Unit, University of Leeds. Data will be made available at the end of the trial. Data will remain available from then on for as long as CTRU retains the data. CTRU makes data available by a 'controlled access' approach. Data will only be released for legitimate secondary research purposes, where the Chief Investigator, Sponsor and CTRU agree that the proposed use has scientific value and will be carried out to a high standard (in terms of scientific rigour and information governance and security), and that there are resources available to satisfy the request. Data will only be released in line with participants' consent, all applicable laws relating to data protection and confidentiality, and any contractual obligations to which the CTRU is subject.