Do Changes in ctDNA Predict Response for Patients With Oesophageal Cancer Receiving Durvalumab

NCT03653052 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: CALIBRATION
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Oesophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical response to therapy (durvalumab)

  Changes in ctDNA levels (from baseline to C1/C2) compared with objective RECIST radiological response at 26 weeks

  26 weeks

Other Outcomes (7)

• Immunological milieu in tumour samples

  33 months

• ctDNA/plasma sampling

  33 months

• ctDNA's potential to identify tumour resistance mechanisms

  33 months

Study Arms (1)

Durvalumab

EXPERIMENTAL

Patients with advanced oesophageal cancer will be administered with 1500mg of durvalumab once every 4 weeks for up to 6 months.

Drug: Durvalumab

Interventions

Durvalumab DRUG

Durvalumab will be administered via an infusion in the arm, over a duration of up to 1 hour.

Also known as: MEDI4736

Durvalumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 v1.1.
• 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
• Haemoglobin ≥ 9.0 g/dL
• AST or ALT ≤ 2.5 times the upper limit of normal (ULN), (except patients with documented liver metastases where AST and/or ALT can be ≤ 5×ULN)
• Serum bilirubin ≤1.5 × ULN. (Except patients with confirmed Gilbert's syndrome)
• INR and APTT ≤ 1.5×ULN.
• Calculated creatinine clearance (CrCl) ≥ 40 mL/min (Cockcroft-Gault formula)

You may not qualify if:

• 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.
• Dermatological: Psoriasis, Lupus/SLE.
• Other: Rheumatoid Arthritis, Hypophysitis, Uveitis.
• History of organ transplant that requires use of immunosuppressive medications or any medical condition in which immunosuppressive agents were administered, including but, not limited to:
• Systemic corticosteroids.
• Methotrexate, azathioprine

Sponsors & Collaborators

• Simon C Pacey, MD: lead
• AstraZeneca: collaborator

Study Sites (1)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, CB2 0QQ, United Kingdom

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Simon Pacey

  Cambridge University Hospitals

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Investigator

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: August 31, 2018
• Study Start: October 30, 2018
• Primary Completion: November 11, 2021
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 24, 2025

Record last verified: 2025-04

Locations

GB (1)