Do Changes in ctDNA Predict Response for Patients With Oesophageal Cancer Receiving Durvalumab (CALIBRATION)
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|ClinicalTrials.gov Identifier: NCT03653052|
Recruitment Status : Recruiting
First Posted : August 31, 2018
Last Update Posted : September 3, 2019
Patients with cancer are increasingly being treated with drugs designed to modulate the response of their immune system, broadly to boost their body's defences against cancer. However, there is an unmet need to identify which patients are unlikely to benefit. Deciding on benefit from therapy uses standard imaging methods (e.g. CT scans), which can take time (months) whereas DNA in the bloodstream could be measured more rapidly.
The main aim of this study is to assess whether changes in the level of circulating tumour DNA (ctDNA) can quickly determine a patients response. This would enable patients to change therapies more quickly if they are not responding and reduce exposure to unnecessary side effects.
|Condition or disease||Intervention/treatment||Phase|
|Oesophageal Cancer||Drug: Durvalumab||Phase 2|
Measuring circulating (plasma) tumour DNA has been described as a 'liquid biopsy' able to study a tumour without invasive biopsy. By measuring ctDNA at different time points the investigators can detect tumour changes that indicate if the patient is responding to treatment or not.
This trial has been designed as a prospective, open label, non-randomised trial where patient with advanced oesophageal cancer will be treated with MEDI4736 (durvalumab), a drug designed to alter the immune system response. Samples will be taken to regularly to measure ctDNA levels and compared to patients response at 6 months when undergoing standard CT scans.
The study will run at a single centre (Addenbrookes Hospital, Cambridge). Nineteen, evaluable, patients will receive durvalumab until progression while detailed studies will assess their tumour and immune response.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||CALIBRATION: An Exploratory Study in Patients With Advanced Oesophageal Malignancies Receiving MEDI4736 (Durvalumab), Investigating Whether Early Changes in Circulating Tumour DNA Can Predict Tumour Response|
|Actual Study Start Date :||October 30, 2018|
|Estimated Primary Completion Date :||May 2021|
|Estimated Study Completion Date :||February 2022|
Patients with advanced oesophageal cancer will be administered with 1500mg of durvalumab once every 4 weeks for up to 6 months.
Durvalumab will be administered via an infusion in the arm, over a duration of up to 1 hour.
Other Name: MEDI4736
- Clinical response to therapy (durvalumab) [ Time Frame: 26 weeks ]Changes in ctDNA levels (from baseline to C1/C2) compared with objective RECIST radiological response at 26 weeks
- Immunological milieu in tumour samples [ Time Frame: 33 months ]Changes in intra-tumoural T-Cell distribution, immunostaining and other biomarkers of immune activation following exposure to durvalumab
- ctDNA/plasma sampling [ Time Frame: 33 months ]Tracking immunological changes and variability in immune-cells (clonality, T-cell receptor, tumour infiltrating lymphocytes) and neoantigens; tumour specific mutation(s); and, blood-based biomarkers following exposure to durvalumab
- ctDNA's potential to identify tumour resistance mechanisms [ Time Frame: 33 months ]Tracking immunological changes and variability in immune-cells (clonality, T-cell receptor, tumour infiltrating lymphocytes) and neoantigens; tumour specific mutation(s); and, blood-based biomarkers following exposure to durvalumab
- Correlation in ctDNA levels and occurrence of clinically related adverse events [ Time Frame: 33 months ]Variations in tumour variant alelle frequencies (VAF) compared with the occurrences of >= Grade 2 treatment related side effects
- Integrate the use of iRECIST criteria [ Time Frame: 33 months ]Compare responses by RECIST and iRECIST criteria
- Patient stratification according to predefined genetic signatures [ Time Frame: 33 months ]Time taken and costs incurred from sample collection through to the generation of data and, the correlation between response to durvalumab and the genetic signature that the patient is assigned to
- Ex-vivo effect of compounds on tumour/cell models [ Time Frame: 33 months ]Ex-vivo response to durvalumab using patient derived model systems
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03653052
|Contact: Calibration Trial Coordinator||01223 email@example.com|
|Contact: Cambridge Cancer Trials Unit - Cancer Theme||01223 firstname.lastname@example.org|
|Cambridge University Hospitals NHS Foundation Trust||Recruiting|
|Cambridge, United Kingdom, CB2 0QQ|
|Contact: Calibration Trial Coordinator 01223 216083 email@example.com|
|Contact: Simon Pacey firstname.lastname@example.org|
|Principal Investigator: Simon Pacey|
|Principal Investigator:||Simon Pacey||Cambridge University Hospitals|