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Gastrooesophageal CancerPhase 2DECIPHERNCT05965479

Developing ctDNA Guided Adjuvant Therapy for Gastrooesophageal Cancer

A Phase 2 study testing Trastuzumab deruxtecan in people with Gastrooesophageal Cancer, run by University of Southampton at 14 sites in United Kingdom.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastrooesophageal Cancer
What is being tested?
Trastuzumab deruxtecan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
14 sitesUnited Kingdom
Study dates
10 Apr 2024to 30 Apr 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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
  • ALT/AST ≤ 3 x ULN
  • Total bilirubin ≤ 1.5 x ULN or < 3 x ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia)
  • Serum albumin ≥ 3.0 g/dl
  • Creatinine clearance ≥ 50 mL/min as calculated using the Cockcroft-Gault equation
  • Adequate clotting function International Normalized Ratio (INR) or prothrombin time and either partial thromboplastin or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN.
  • Reproduction:
  • Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilised male partner.
  • For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available at the screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of IMP.
  • Women of childbearing potential are defined as those who are not surgically sterile (i.e., underwent bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal.
  • Women aged <50 years will be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the site.
  • Women aged ≥ 50 years will be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses >1 year ago.
  • Female participants of childbearing potential who are sexually active with a non-sterilised male partner must use at least one highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 7 months after the last dose of IMP. Not all methods of contraception are highly effective.
  • Female participants must refrain from breastfeeding and must not donate (or retrieve their own for use) ova, from the time of screening, throughout the study treatment period, and for at least 7 months after the last dose of IMP.
  • Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is in line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasion abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
  • Non-sterilised male participants who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose of IMP.
  • It is strongly recommended for the female partners of a male participant to also use at least one highly effective method of contraception throughout this period. In addition, male participants should refrain from fathering a child or freezing or donating sperm from screening, throughout the study treatment period, and for at least 4 months after the last dose of IMP.
  • Investigators should advise male participants on the conservation of sperm prior to starting treatment because of the possibility of irreversible infertility/testicular damage due to IMP administered in this study.
  • Female subjects must not donate, or retrieve for their own use, ova from the time of enrolment and throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova prior to enrolment in this study, can be discussed with the patient if clinically appropriate to do so.

Who cannot join

  • 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.)
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  • 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
  • Involvement in the planning and/or conduct of the study
  • Has substance abuse or any other medical conditions, that may, in the opinion of the investigator, interfere with the subjects participation in the clinical study or evaluation of the clinical study results
  • Receipt of live, attenuated vaccine within 30 days prior to the first dose of trastuzumab deruxtecan. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IMP
  • Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Patients positive for hepatitis (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Judgement by the Investigator that the participant should not participate in the study, if the participant is unlikely to comply with study procedures, restrictions, and requirements.

Trial locations and contacts

14 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Elizabeth Smyth contact

023 81205773

elizabeth.smyth2@nhs.net

Daniel Griffiths contact

02381205154

decipher@soton.ac.uk

14 sites in 1 country

United Kingdom14 sites, 14 recruiting

  • Belfast Health and Social Care Trust, Belfast City Hospital

    Belfast, BT9 7AB

    Richard Turkington

    Richard Turkington

    Recruiting

  • Cambridge University Hospital NHS Foundation Trust, Addenbrookes Hospital

    Cambridge, CB2 0QQ

    Hugo Ford

    Hugo Ford

    Recruiting

  • University Hospitals Coventry and Warwickshire, University Hospital Coventry

    Coventry, Warwickshire, CV2 2DX

    Hannah Tween

    Hannah Tween

    Recruiting

  • University Hospitals of Derby and Burton NHS Foundation Trust, Royal Derby Hospital

    Derby, DE22 3NE

    Jessica Davies

    Jessica Davies

    Recruiting

  • NHS Tayside, Ninewells Hospital

    Dundee, DD2 1UB

    Russell Petty

    Russell Petty

    Recruiting

  • Royal Surrey NHS Foundation Trust, Royal Surrey County Hospital

    Guildford, Surrey, GU2 7XX

    Madeleine Hewish

    Madeleine Hewish

    Not yet recruiting

  • Hull University Teaching Hospitals NHS Trust, Castel Hill Hospital

    Hull, HU16 5JQ

    Rajarshi Roy

    Rajarshi Roy

    Recruiting

  • Leeds Teaching Hospitals NHS Trust, St James's University Hospital

    Leeds, LS9 7TF

    Daniel Swinson

    Daniel Swinson

    Recruiting

  • University College London Hospitals NHS Foundation Trust, University College Hospital London

    London, NW1 2BU

    John Bridgewater

    John Bridgewater

    Recruiting

  • Guys & St Thomas NHS Foundation Trust, Guy's Hospital

    London, SE1 9RT

    Sarah Ngan

    Sarah Ngan

    Recruiting

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

    Was Mansoor

    Was Mansoor

    Recruiting

  • Oxford University Hospitals NHS Trust, Churchill Hospital

    Oxford, OX3 7LE

    Elizabeth Smyth

    Elizabeth Smyth

    Recruiting

  • Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital

    Preston, PR2 9HT

    Catherine Mitchell

    Catherine Mitchell

    Recruiting

  • Velindre University NHS Trust, Velindre Cancer Centre

    Whitchurch, CF14 2TL

    Carys Morgan

    Carys Morgan

    Not yet recruiting

Other trials in United Kingdom

About this study

Official title: A Single Arm Phase II Trial of Trastuzumab Deruxtecan in Patients With Gastrooesophageal Adenocarcinoma Cancer Who Are ctDNA and HER2 Positive

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.

Read the detailed description

Gastrooesophageal (GOA) cancer is a common, global cancer which often presents at an advanced stage. Those diagnosed early will generally have neoadjuvant treatment with FLOT chemotherapy followed by surgery followed by the same FLOT chemotherapy post surgery. Treatment however is curative in less than 50%.

Circulating tumour DNA (ctDNA) is found in the bloodstream. It refers to DNA that comes from cancerous cells and tumours. If ctDNA is positive it means that there are microscopic traces of tumour in the bloodstream (minimal residual disease). Patients who are ctDNA positive after chemotherapy and surgery are less likely to benefit from further FLOT chemotherapy and more likely to relapse.

HER2 positive describes cells that have a protein called HER2 on their surface. In normal cells, HER2 helps control cell growth. Cancer cells that make too much HER2 may grow more quickly and are more likely to spread to other parts of the body.

Trastuzumab deruxtecan (T-DXd) is an antibody that targets HER2 cells. It attaches to the HER2 cells on the tumour and destroys them. In the UK, trastuzumab deruxtecan (Enhertu) is currently offered to patients with advanced breast cancer who are HER2 positive. In the US, Israel and Japan it is licenced in patients with advanced HER2 positive GOA.

DECIPHER aims to treat patient's with GOA post-surgery who are both HER2 and ctDNA positive with trastuzumab deruxtecan (Enhertu) instead of standard care FLOT chemotherapy. The aim of the trial is to treat the minimal residual disease reducing the chance of relapse. All trial patients will be followed for up to 2 years to record their response to treatment. 25 patients will be recruited over 18 months.

Patients will be treated with 6.4 mg/kg trastuzumab deruxtecan every 21 days for 8 cycles.

Being tested
Trastuzumab deruxtecan
Keywords
Gastrooesophageal adenocarcinoma, Oesophageal cancer, Gastric cancer, HER2, ctDNA, Minimal residual disease
Medical subject headings
Esophageal Neoplasms, Stomach Neoplasms, Neoplasm, Residual

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Trastuzumab deruxtecanDrug

    Also called Enhertu

    Trastuzumab deruxtecan is an antibody-drug conjugate that contains trastuzumab covalently linked to deruxtecan, a topoisomerase I inhibitor. It is given by intravenous infusion.

Study groups in NCT05965479
Study groupRoleWhat they receive
Trastuzumab deruxtecanExperimentalParticipants 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.
Receives: Drug: Trastuzumab deruxtecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ctDNA clearance

    Percentage of people who are classed ctDNA negative, as measured by the Signatera assay

    Measured: At the end of Cycle 4 (each cycle is 21 days)

Secondary outcomes (7)

  1. ctDNA clearance (yes/no)

    Percentage of people who are ctDNA negative after each cycle

    Measured: Up to completion of cycle 8 (where each cycle is 21 days)

  2. Disease Free Survival

    Time from surgery to recurrence of macroscopic disease of radiological imaging or death

    Measured: At 12 months and 24 months

  3. Overall survival

    Time from surgery to death

    Measured: 12, 18 and 24 months

  4. QLQ-C30

    Quality of life scored from QLQ-C30

    Measured: Up to 30 months post surgery

  5. QLQ-OG25

    Quality of life scored from QLQ-OG25

    Measured: Up to 30 months post surgery

  6. EQ-5D-5L

    Quality of life scored from EQ-5D-5L

    Measured: Up to 30 months post surgery

  7. Safety and tolerability of T-DXd

    Frequency of adverse events and percentage of people experiencing them

    Measured: Up to 100 days post last dose of trial treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2023
  2. Study start10 Apr 2024
  3. Primary completion31 Mar 2026 (estimated)
  4. Study completion30 Apr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05965479
Sponsor's protocol ID
68838
Other IDs
2022-003445-34
Acronym
DECIPHER
Status last verified
Nov 2024
First submitted
6 Jul 2023
Last updated
12 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Trastuzumab deruxtecan in people with Gastrooesophageal Cancer, run by University of Southampton at 14 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 33 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 12 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Elizabeth Smyth (023 81205773, elizabeth.smyth2@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ctDNA clearance (time frame: At the end of Cycle 4 (each cycle is 21 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05965479.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2024.

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