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
Overview
- Phase
- Phase 2
- Intervention
- Durvalumab
- Conditions
- Oesophageal Cancer
- Sponsor
- Simon C Pacey, MD
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Clinical response to therapy (durvalumab)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Simon C Pacey, MD
Chief Investigator
Cambridge University Hospitals NHS Foundation Trust
Eligibility Criteria
Inclusion Criteria
- •Provide written, informed consent to participate
- •Aged ≥ 18 years at time of consent
- •Confirmed advanced oesophageal cancer for which the patient must have received at least one prior line of standard of care treatment
- •Predicted life expectancy ≥ 3 months
- •Eastern Cooperative Oncology Group (ECOG) PS 0 or 1
- •Measurable disease, as defined by RECIST v1.
- •In the investigator's opinion, have an accessible and biopsiable tumour lesion for additional research biopsy, to which the patient will have to consent at screening.
- •Adequate hematologic and organ function, defined by:
- •ANC ≥ 1500 cells/μL (no GCSF support 2 weeks prior to trial entry)
- •Platelet count ≥ 100,000/μL
Exclusion Criteria
- •Weight of ≤30kg
- •Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
- •Participation in other clinical trials involving active treatment for the malignant disease.
- •Received radiotherapy treatment on a wide body field, or an equivalent to more than 30% of the bone marrow, within the last 4 weeks.
- •Any unresolved symptom NCI CTCAE Grade ≥2 from previous anticancer therapy (with the exception of alopecia and vitiligo).
- •Active or prior documented autoimmune or inflammatory disease (except vitiligo) within the last 3 years, for example:
- •Intestinal: Inflammatory Bowel Disease (Colitis, Crohn's Disease), Diverticulitis (with the exception of Diverticulosis), Coeliac Disease, Irritable Bowel Disease
- •Vascular: any type of Vasculitic disorder, i.e.: Wegner syndrome.
- •Endocrine: any endocrine alteration related to an auto-immune process i.e.: Hashimoto syndrome. NOTE: patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement treatment may be included at the discretion of the CI.
- •Respiratory: Active Pneumonitis (of any origin: inflammatory or infectious), Sarcoidosis.
Arms & Interventions
Durvalumab
Patients with advanced oesophageal cancer will be administered with 1500mg of durvalumab once every 4 weeks for up to 6 months.
Intervention: Durvalumab
Outcomes
Primary Outcomes
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