Developing ctDNA Guided Adjuvant Therapy for Gastrooesophageal Cancer
DECIPHER
A Single Arm Phase II Trial of Trastuzumab Deruxtecan in Patients With Gastrooesophageal Adenocarcinoma Cancer Who Are ctDNA and HER2 Positive
2 other identifiers
interventional
25
1 country
14
Brief Summary
Multicentre, single arm, open label UK phase II trial to assess the efficacy of trastuzumab deruxtecan in reducing micrometastatic disease burden in HER2 positive GOA patients who are ctDNA positive after chemotherapy and surgery. 25 patients will be recruited from approximately 15 NHS secondary care sites.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Apr 2024
Typical duration for phase_2
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
July 6, 2023
CompletedFirst Posted
Study publicly available on registry
July 28, 2023
CompletedStudy Start
First participant enrolled
April 10, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
April 30, 2028
ExpectedNovember 12, 2024
November 1, 2024
2 years
July 6, 2023
November 7, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
ctDNA clearance
Percentage of people who are classed ctDNA negative, as measured by the Signatera assay
At the end of Cycle 4 (each cycle is 21 days)
Secondary Outcomes (7)
ctDNA clearance (yes/no)
Up to completion of cycle 8 (where each cycle is 21 days)
Disease Free Survival
At 12 months and 24 months
Overall survival
12, 18 and 24 months
QLQ-C30
Up to 30 months post surgery
QLQ-OG25
Up to 30 months post surgery
- +2 more secondary outcomes
Other Outcomes (2)
Measurement of the quantity of ctDNA present in blood using the Signatera assay
From date of surgery until the date of recurrence or date of death from any cause, whichever comes first, assessed up to 30 months
Measurement of the quantity of ctDNA present in blood using Signatera assay
From date of surgery until the date of recurrence or date of death from any cause, whichever comes first, assessed up to 30 months
Study Arms (1)
Trastuzumab deruxtecan
EXPERIMENTALParticipants in the study will be treated with trastuzumab deruxtecan at a dose of 6.4 mg/kg intravenously every 21 days for 8 cycles. If required, patients may dose reduce to level -1 or level -2: * Dose level 0 is 6.4 mg/kg intravenously every 21 days * Dose level -1 is 5.4 mg/kg intravenously every 21 days * Dose level -2 is 4.4 mg/kg intravenously every 21 days T-DXd will be administered using an IV bag containing 5% (w/v) Dextrose Injection infusion solution and delivered through an IV administration set with a 0.2 or 0.22 μm filter. The standard infusion time for T-DXd is approximately 90 minutes +/- 10 minutes for the first infusion. If the first infusion is well tolerated and the participant does not experience an infusion-related reaction, then the minimum infusion time for subsequent cycles is 30 minutes. However, if there are interruptions during the infusion, the total time must not exceed 3 hours at room temperature.
Interventions
Trastuzumab deruxtecan is an antibody-drug conjugate that contains trastuzumab covalently linked to deruxtecan, a topoisomerase I inhibitor. It is given by intravenous infusion.
Eligibility Criteria
You may qualify if:
- Pathologically documented adenocarcinoma of the stomach (clinical stage before surgery of AJCC I-III), gastroesophageal junction, or lower oesophagus (to include Type I Siewert only), with HER2 overexpression (IHC 3+ or IHC 2+/ISH+) based on local tissue testing results.
- ctDNA positive after surgery as per Signatera assay
- Capable of giving signed informed consent prior to any mandatory study specific procedures, sampling, or analyses and which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
- Male and female participants must be at least 18 years of age at the time of signing the ICF.
- Treated with neoadjuvant chemotherapy before surgery for at least six weeks.
- Surgical resection with clear margins (R0).
- Recovered from surgery in the opinion of the investigator.
- No previous treatment with trastuzumab or other HER2 directed therapy.
- No evidence of metastatic disease on post-surgical CT.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
- Has LVEF ≥ 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before treatment.
- Has adequate organ and bone marrow function within 14 days before treatment allocation as below:
- Platelet count ≥ 100x109/L (Platelet transfusion is not allowed within 1 week prior to screening assessment, use of thrombopoietin receptor agonists is not allowed within 2 weeks prior to screening assessment)
- Haemoglobin ≥ 80 g/L. Participants requiring transfusions or growth factor support to maintain haemoglobin ≥ 80 g/L are not eligible. (Red blood cell transfusions is not allowed within 1 week prior to screening assessment)
- Absolute neutrophil count ≥ 1.5 x 109/L (granulocyte-colony stimulating factor \[G-CSF\] administration is not allowed within 1 week prior to screening assessment
- +18 more criteria
You may not qualify if:
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AE's, or compromise the ability of the participant to give written informed consent.
- Participants with a medical history of myocardial infarction within 6 months before treatment or symptomatic CHF (New York Heart Association Class II to IV), unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (\<6 months) cardiovascular event, including myocardial infarction, unstable angina pectoris, and stroke. Participants with troponin levels above ULN at screening (as defined by the manufacturer)m and without myocardial related symptoms, should have a cardiologic consultation before enrolment to rule out myocardial infarction.
- Corrected QT interval (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG
- History of (non-infectious) ILD/pneumonitis, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Any of the following:
- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g., clinically significant pulmonary emboli within 3 months of treatment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, clinically significant pleural effusion etc.)
- Any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's, sarcoidosis etc.), where there is documented, or a suspicion of, pulmonary involvement at the time of screening
- Prior pneumonectomy (complete)
- Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals
- Multiple primary malignancies within the prior 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumours curatively treated.
- A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt.
- Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline. The following exemption will apply; stable chronic G2 toxicity which in the opinion of the investigator is not reasonably expected to be exacerbated by treatment with study drugs.
- Known allergy or hypersensitivity to T-DXd or any of the study drug components
- History of severe hypersensitivity reactions or other monoclonal antibodies
- Pregnant or breastfeeding female participants, or participants who are planning to become pregnant
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Southamptonlead
- AstraZenecacollaborator
- Natera, Inc.collaborator
Study Sites (14)
Royal Surrey NHS Foundation Trust, Royal Surrey County Hospital
Guildford, Surrey, GU2 7XX, United Kingdom
University Hospitals Coventry and Warwickshire, University Hospital Coventry
Coventry, Warwickshire, CV2 2DX, United Kingdom
Belfast Health and Social Care Trust, Belfast City Hospital
Belfast, BT9 7AB, United Kingdom
Cambridge University Hospital NHS Foundation Trust, Addenbrookes Hospital
Cambridge, CB2 0QQ, United Kingdom
University Hospitals of Derby and Burton NHS Foundation Trust, Royal Derby Hospital
Derby, DE22 3NE, United Kingdom
NHS Tayside, Ninewells Hospital
Dundee, DD2 1UB, United Kingdom
Hull University Teaching Hospitals NHS Trust, Castel Hill Hospital
Hull, HU16 5JQ, United Kingdom
Leeds Teaching Hospitals NHS Trust, St James's University Hospital
Leeds, LS9 7TF, United Kingdom
University College London Hospitals NHS Foundation Trust, University College Hospital London
London, NW1 2BU, United Kingdom
Guys & St Thomas NHS Foundation Trust, Guy's Hospital
London, SE1 9RT, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Oxford University Hospitals NHS Trust, Churchill Hospital
Oxford, OX3 7LE, United Kingdom
Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital
Preston, PR2 9HT, United Kingdom
Velindre University NHS Trust, Velindre Cancer Centre
Whitchurch, CF14 2TL, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Elizabeth Smyth
University of Oxford
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 6, 2023
First Posted
July 28, 2023
Study Start
April 10, 2024
Primary Completion
March 31, 2026
Study Completion (Estimated)
April 30, 2028
Last Updated
November 12, 2024
Record last verified: 2024-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Anonymous data will be available for request from 3 months after the publication of the results to researchers who provide a completed data sharing request form that describes a methodologically sound proposal, for the purpose of the approved proposal and if appropriate, signed a data-sharing agreement.
- Access Criteria
- Data access requests will be reviewed against specific eligibility criteria by the SCTU data custodian and key members of the trial team.
IPD will be made available, including data dictionaries, for approved data sharing requests. Individual participant data will be shared that underlie the results after de-identification and normalisation of information (text, tables, figures, and appendices). The study protocol and statistical analysis plan will also be available. Pseudonymised participant data within the clinical trial dataset will be available for sharing via controlled access by authorised Southampton Clinical Trials Unit (SCTU) staff. The request for data access will need to detail the specific requirements and the proposed research, statistical analysis, publication plan and evidence of research group qualifications. Data will be shared once all parties have signed relevant data sharing documentation covering SCTU conditions for sharing and if required, an additional data sharing agreement from the sponsor. Proposals should be directed to ctu@soton.ac.uk.