We'd like your feedback
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Prof
Sarah
Brown
+44 (0)113 343 1477
Ctru_concorde@leeds.ac.uk
Mr
Jamie
Oughton
+44 (0)113 3431494
Ctru_concorde@leeds.ac.uk
Non small cell lung cancer
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Background and study aims
This study will investigate if drug treatment makes radiotherapy a more effective treatment for non-small cell lung cancer (NSCLC) that has not spread beyond the chest. This study aims to see which dose of the drug is safe to use.
DNA carries the instructions for making our body. Radiotherapy works by damaging the cancer cells’ DNA to the point where hopefully they can no longer survive. The cancer cell will try to repair the radiotherapy damage, so blocking these repair systems may make radiotherapy more effective.
The drugs being evaluated in this study are called DNA damage response inhibitors (DDRis), they limit the body’s ability to repair damaged DNA. It is believed that this will cause the radiotherapy to kill more cancer cells. However, radiotherapy can also damage the DNA of the normal non-cancer cells surrounding the tumour. It is important to work out whether using DDRi with radiotherapy leads to increased side-effects or not. DDRis have been given with radiotherapy and chemotherapy in a number of tumour types, including lung cancer. We are also including
immunotherapy treatment in some study-arms. Immunotherapy is a drug treatment
administered into a vein that helps the patient’s immune system fight cancer cells. Both patients and study doctors will know prior to the start of the actual treatment whether a DDRi with or
without immunotherapy will be given, and if so which one.
The main purpose of the study is to find the most suitable dose of the DDRi that can be safely combined with radiotherapy. This will enable us to test this dose in larger clinical studies. This study will also be looking at whether the DDRis might improve the effectiveness of the radiotherapy in treating the cancer. Samples from participant’s tumour and blood will be tested to see if patients who might benefit from the DDRi can be identified. Several DDRis are being examined in the study, each in a separate study-arm. Participants will only be enrolled into one study arm.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
2020 Protocol article in https://pubmed.ncbi.nlm.nih.gov/33072895/ protocol2022 Other publications in https://pubmed.ncbi.nlm.nih.gov/36446040/ (added 02/12/2022)
You can take part if:
Current inclusion criteria as of 12/01/2024:
Core inclusion criteria (radiation phase):
1. 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)
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. 60 Gy) 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 years
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 (WOCBP)/6 months for men after trial treatment
completion. Treatment is defined as including the last dose of durvalumab or DDRi in the consolidation phase (or comply with more stringent contraceptive requirements if prescribed in the relevant study-arm protocol).
14. Adequate organ function within 28 days prior to confirmation of eligibility and 7 days of study treatment
15. Patient has body weight of >30 kg
Inclusion criteria (consolidation phase):
The following eligibility criteria must be met before participants can receive durvalumab +/- DDRi in the consolidation phase. Participants that do not meet these criteria to enter the consolidation phase, or are not in a study arm with durvalumab +/- DDRi consolidation will continue post RT follow up.
Participants randomised to RT + DDRi in the radiation phase are eligible to receive both DDRi and durvalumab in consolidation phase. Participants will not be permitted to receive DDRi alone. Participants randomised to RT + DDRi that have a DLT and meet the consolidation eligibility criteria can receive durvalumab alone.
Participants randomised to RT-only in the radiation phase are eligible to receive durvalumab alone in the consolidation phase if they meet the following eligibility criteria.
1. A minimum of 4 and a maximum of 8 weeks have elapsed following completion of RT. (Investigators should ideally aim to start consolidation treatment within 6 weeks, following the receipt of the CT scan results to rule out progression.)
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 are met
5. Patient has no known hypersensitiv
You may not be able to take part if:
Current exclusion criteria as of 31/03/2023:Core exclusion criteria (radiation phase):1. Mixed non-small cell and small cell tumours2. Confirmed progressive disease according to RECIST 1.1 during induction chemotherapy3. Participation in a study of an investigational agent or using an investigational device within 4 weeks prior to the anticipated start of treatment4. Current or previous malignant disease which may impact on a patient’s estimated life expectancy (other than NSCLC)5. History of interstitial pneumonitis (to include diffuse alveolar damage, non-malignant causes of pneumonitis, acute respiratorydistress syndrome, alveolitis, cryptogenic organising pneumonia, obliterative bronchiolitis, non-malignant causes of pulmonary fibrosis, usual interstitial pneumonia, interstitial pulmonary fibrosis and connective tissue disorder (scleroderma, systemic lupus erythematosus))6. Prior thoracic radiotherapy (excluding patients that have had RT for breast cancer or lung SABR to the contralateral lung providing that the overlap is minimal as per local investigator's discretion or as discussed and agreed by CI/Study Arm Lead contacted via CTRU as required)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 (ECGs) (QTc interval will be calculated using Fridericia’s formula). Multiple ECGs are only required if 1st ECG QTcF >470 msec. ECGs should be at least 5 minutes apart.9. Received a prior autologous or allogeneic organ or tissue transplantation10. 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 inflammatorybowel disease, refractory nausea and vomiting etc).11.Grade 2 or higher peripheral sensory neuropathy.12. Known positive test for human immunodeficiency virus (HIV), history of active primary immunodeficiency, known active hepatitis B or C infection (new test not mandated for trial entry). Participants with a past or resolved hepatitis B virus infection are eligible (defined as the presence of the hepatitis B core antibody (antiHBc) and absence of the hepatitis B surface antigen (HBsAg). Participants positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.13. Positive pregnancy test (at eligibility assessment for women of childbearing potential) or breast-feeding women14. Patients with persistent toxicities (>CTCAE grade 2) caused by previous cancer therapy, excluding alopecia15. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML16. Major surgery within 2 weeks of confirmation of eligibility17. 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, known active Mycobacteria tuberculosis infection, any psychiatric disorder that prohibits obtaining informed consent.18. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (eg, ulcerative colitis or Crohn’s disease), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis rheumatoid arthritis, hypophysitis, uveitis, etc)). The following are exceptions to this criterion: patients with vitiligo or alopecia, patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement, any chronic skin condition that does not require systemic therapy, patients without active disease in the last 5 years at enrolment may be included but only after consultation with the CI/Study arm-lead (via CTRU), patients with coeliac disease controlled by diet alone.19. Exclusions as described in the relevant study arm protocol. Patients ineligible for a particular study arm may be considered for entry into an alternative study arm if an appropriate slot is available and they meet all the inclusion and exclusion criteria for that arm. This will need to be discussed with CTRU and the patient will be required to reconsent using the appropriate study arm PIS/ICF.
Exclusion criteria (consolidation phase):1. Progressive disease during RT or at the end of RT treatment response assessment (4-week post RT CT scan must be reviewed prior to entry for the consolidation phase)2. Participant declines treatment in the consolidation phase3. Patients who have received prior anti-PD-1 or anti PD-L1 treatment4. Major surgery within 4 weeks of confirmation of eligibility for consolidation phase5. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent, steroids as premedication for hypersensitivity reactions or as protocol defined pre-medication (e.g. as anti-emetics for trial treatments or for CT scan premedication).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. Examples include, but are not limited to, symptomatic congestive heart failure,unstable angina pectoris, uncontrolled cardiac arrhythmia, uncontrolled hypertension, uncontrolled atrial fibrillation, active bleeding, recent (within 3 months) myocardial infarction, major seizure, active COVID-19 (defined in radiation phase eligibility criteria), known activeMycobacteria tuberculosis infection, serious chronic gastrointestinal conditions associated with diarrhoea, or any psychiatric disorder that prohibits obtaining informed consent.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). The following are exceptions to this criterion: Patients with vitiligo or alopecia, patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement, any chronic skin condition that does not require systemic therapy, patients without active disease in the last 5 years may be included but only after consultation with the study arm lead/CI (contacted via CTRU), patients with celiac disease controlled by diet alone._____
Previous exclusion criteria:1. Mixed non-small cell and small cell tumours2. Confirmed progressive disease during induction chemotherapy3. Participation in a study of an investigational agent or using an investigational device within 4 weeks prior to the anticipated start of treatment4. Current or previous malignant disease which may impact on a patient’s estimated life expectancy (other than NSCLC)5. History of interstitial pneumonitis6. Prior thoracic radiotherapy (excluding patients that have had RT for breast cancer providing that the overlap is minimal as per local investigators discretion or as discussed and agreed by CI as required) 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 (ECGs).9. Received a prior autologous or allogeneic organ or tissue transplantation10. 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 neuropathy12. Known positive test for human immunodeficiency virus (HIV), active hepatitis B or C infection (new test not mandated for trial entry)13. Positive pregnancy test (at eligibility assessment for women of childbearing potential) or breast-feeding women14. Patients with persistent toxicities (> CTCAE grade 2) caused by previous cancer therapy, excluding alopecia15. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML16. Major surgery within 2 weeks of confirmation of eligibility17. 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.14. Gemcitabine treatment (within 6 months of assessment of eligibility15. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (eg, ulcerative colitis or Crohn’s disease), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis, Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc)). The following are exceptions to this criterion:15.1. Patients with vitiligo or alopecia15.2. Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement15.3. Any chronic skin condition that does not require systemic therapy15.4. Patients without active disease in the last 5 years at enrolment may be included but only after consultation with the CI/Study arm-lead15.5. Patients with coeliac disease controlled by diet alone16. Exclusions as described in the relevant study arm protocol
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Mr
Jamie
Oughton
+44 (0)113 3431494
Ctru_concorde@leeds.ac.uk
Prof
Sarah
Brown
+44 (0)113 343 1477
Ctru_concorde@leeds.ac.uk
The study is sponsored by University of Leeds and funded by Cancer Research UK; National Institute for Health Research (NIHR) (UK); AstraZeneca.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
Or CPMS 45504
You can print or share the study information with your GP/healthcare provider or contact the research team directly.
