Trial Title:
Developing ctDNA Guided Adjuvant Therapy for Gastrooesophageal Cancer
NCT ID:
NCT05965479
Condition:
Gastrooesophageal Cancer
Conditions: Official terms:
Trastuzumab
Trastuzumab deruxtecan
Conditions: Keywords:
Gastrooesophageal adenocarcinoma
Oesophageal cancer
Gastric cancer
HER2
ctDNA
Minimal residual disease
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Trastuzumab deruxtecan
Description:
Trastuzumab deruxtecan is an antibody-drug conjugate that contains trastuzumab covalently
linked to deruxtecan, a topoisomerase I inhibitor. It is given by intravenous infusion.
Arm group label:
Trastuzumab deruxtecan
Other name:
Enhertu
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.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- 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.
I. 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.
II. 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.
Exclusion Criteria:
- 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:
1. 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.)
2. 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
3. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Royal Surrey NHS Foundation Trust, Royal Surrey County Hospital
Address:
City:
Guildford
Zip:
GU2 7XX
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Madeleine Hewish
Investigator:
Last name:
Madeleine Hewish
Email:
Principal Investigator
Facility:
Name:
University Hospitals Coventry and Warwickshire, University Hospital Coventry
Address:
City:
Coventry
Zip:
CV2 2DX
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Hannah Tween
Investigator:
Last name:
Hannah Tween
Email:
Principal Investigator
Facility:
Name:
Belfast Health and Social Care Trust, Belfast City Hospital
Address:
City:
Belfast
Zip:
BT9 7AB
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Richard Turkington
Investigator:
Last name:
Richard Turkington
Email:
Principal Investigator
Facility:
Name:
Cambridge University Hospital NHS Foundation Trust, Addenbrookes Hospital
Address:
City:
Cambridge
Zip:
CB2 0QQ
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Hugo Ford
Investigator:
Last name:
Hugo Ford
Email:
Principal Investigator
Facility:
Name:
University Hospitals of Derby and Burton NHS Foundation Trust, Royal Derby Hospital
Address:
City:
Derby
Zip:
DE22 3NE
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Jessica Davies
Investigator:
Last name:
Jessica Davies
Email:
Principal Investigator
Facility:
Name:
NHS Tayside, Ninewells Hospital
Address:
City:
Dundee
Zip:
DD2 1UB
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Russell Petty
Investigator:
Last name:
Russell Petty
Email:
Principal Investigator
Facility:
Name:
Hull University Teaching Hospitals NHS Trust, Castel Hill Hospital
Address:
City:
Hull
Zip:
HU16 5JQ
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Rajarshi Roy
Investigator:
Last name:
Rajarshi Roy
Email:
Principal Investigator
Facility:
Name:
Leeds Teaching Hospitals NHS Trust, St James's University Hospital
Address:
City:
Leeds
Zip:
LS9 7TF
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Daniel Swinson
Investigator:
Last name:
Daniel Swinson
Email:
Principal Investigator
Facility:
Name:
University College London Hospitals NHS Foundation Trust, University College Hospital London
Address:
City:
London
Zip:
NW1 2BU
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
John Bridgewater
Investigator:
Last name:
John Bridgewater
Email:
Principal Investigator
Facility:
Name:
Guys & St Thomas NHS Foundation Trust, Guy's Hospital
Address:
City:
London
Zip:
SE1 9RT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Sarah Ngan
Investigator:
Last name:
Sarah Ngan
Email:
Principal Investigator
Facility:
Name:
The Christie NHS Foundation Trust
Address:
City:
Manchester
Zip:
M20 4BX
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Was Mansoor
Investigator:
Last name:
Was Mansoor
Email:
Principal Investigator
Facility:
Name:
Oxford University Hospitals NHS Trust, Churchill Hospital
Address:
City:
Oxford
Zip:
OX3 7LE
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Elizabeth Smyth
Investigator:
Last name:
Elizabeth Smyth
Email:
Principal Investigator
Facility:
Name:
Lancashire Teaching Hospitals NHS Foundation Trust, Royal Preston Hospital
Address:
City:
Preston
Zip:
PR2 9HT
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Catherine Mitchell
Investigator:
Last name:
Catherine Mitchell
Email:
Principal Investigator
Facility:
Name:
Velindre University NHS Trust, Velindre Cancer Centre
Address:
City:
Whitchurch
Zip:
CF14 2TL
Country:
United Kingdom
Status:
Not yet recruiting
Contact:
Last name:
Carys Morgan
Investigator:
Last name:
Carys Morgan
Email:
Principal Investigator
Start date:
April 10, 2024
Completion date:
April 30, 2028
Lead sponsor:
Agency:
University of Southampton
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Collaborator:
Agency:
Natera, Inc.
Agency class:
Industry
Source:
University of Southampton
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05965479
