Gastric CancerPhase 2TRINITYNCT06253650
Adjuvant TRastuzumab Deruxtecan for HER2-positive Gastroesophageal Cancer With Persistence of miNImal Residual Disease
A Phase 2 study testing Experimental in people with Gastric Cancer and HER2-positive Gastric Cancer, run by Gruppo Oncologico del Nord-Ovest at 1 site in Italy.
Trial summary
TRINITY is designed as a multicentre, randomized, open-label, interventional phase II study aimed at investigating the activity, efficacy and safety of trastuzumab-deruxtecan (T-DXd) plus capecitabine/5-fluorouracil as a post-operative treatment in localized/locally advanced gastric or gastroesophageal junction cancer… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastric Cancer, HER2-positive Gastric Cancer
- What is being tested?
- Experimental
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteItaly
- Study dates
- 1 Mar 2024to 1 Mar 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
- Written informed consent and any locally required authorization (such as the European Union [EU] Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- Compliance with all the study procedures and treatments. Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating Centre.
- Age ≥ 18 years old.
- Eastern Cooperative Oncology group (ECOG) Performance Status 0-1.
- Life expectancy of at least 12 weeks.
- Resected gastric or gastroesophageal junction (Siewert I-II-III) cancer/esophageal adenocarcinoma, after the completion of pre-operative chemotherapy with FLOT, as per standard clinical practice.
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- Absence of distant metastases as defined by post-operative radiological assessments (contrast-enhanced CT scan of the thorax and abdomen or, in case of contraindications, non-contrast-enhanced chest CT scan and abdomen Magnetic Resonance Imaging)
- Presence of locally determined HER2 overexpression/amplification on the post-treatment surgical tissue specimen defined as IHC 3+ or 2+/ISH amplified.
- Positivity of the post-operative liquid biopsy, performed 2-6 weeks after the radical surgery.
- LVEF ≥ 50% within 28 days before randomization/enrolment.
- Adequate bone marrow and organ function within 14 days before randomization/enrolment as described below:
- Neutrophil count ≥ 1.5 x 10^3/μL
- Platelet count ≥ 100 x 10^6/μL
- Haemoglobin ≥ 9 g/dL
- Total bilirubin lower than 1.5 time the upper-normal limits (ULN) of the Institutional normal values
- AST (SGOT) and/or ALT (SGPT) <3 x ULN
- serum albumin ≥ 2.5 g/dL
- Creatinine clearance (calculated according to Cockroft and Gault) > 60 mL/min
- International normalised ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN
- Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized 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 will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
- Female patients of childbearing potential who are sexually active with a non-sterilized 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 patients must refrain from breastfeeding while on study and for 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 line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable.
- Non-sterilized male patients 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 for T-DXd while 6 months for docetaxel and oxaliplatin. 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 occasional abstinence, the rhythm method, and the withdrawal method are not acceptable. It is strongly recommended for the female partners of a male patient to also use at least one highly effective method of contraception throughout this period. In addition, male patients should refrain from fathering a child, or freezing or donating sperm from the time of randomisation/enrolment, throughout the study and for 4 months after the last dose of IMP for T-DXd while 6 months for docetaxel and oxaliplatin. Preservation of sperm should be considered prior to enrollment in this study.
- Female subjects must not donate, or retrieve for their own use, ova from the time of randomization/enrolmentand 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 may be considered prior to enrollment in this study.
Who cannot join
- Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
- Participation in another clinical study with an investigational product during the last 12 months
- Signs of distant metastases at any site.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, renal disease, neurological disease or peripheral neuropathy, serious chronic gastrointestinal conditions associated with diarrhea, or substance abuse or any other medical or psychiatric illness/social situations that in the opinion of the investigator would limit compliance with study requirement, interfere with the subject's participation in the clinical study, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent or interfere with the evaluation of the clinical study results.
- Patients with a medical history of myocardial infarction (MI) within 6 months before randomization/enrolment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI.
- Corrected QT interval (QTcF) prolongation to > 470 msec (females) or >450 msec (males) based on average of the screening triplicate12-lead ECG.
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- History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
- Lung criteria:
- Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.)
- Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.
- Prior pneumonectomy (complete)
- Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
- Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection not under adequate disease control (that is defined as the presence of all the following conditions: receiving stable regimen of highly active anti-retroviral therapy for at least 4 weeks prior to study enrollment, CD4+ count above 250 cells/μL, undetectable viral load on standard polymerase chain reaction-based tests, absence of any HIV-related opportunistic infections for at least 4 weeks prior to study enrollment and no requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections), or active hepatitis B or C infection (HBsAg, anti-HBs, anti-HBc, anti-HCV). Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Patients who are anti-HBc positive and HBsAg negative or patients with HBsAg positive have to dose HBV-DNA. If HBV DNA is undetectable (<10UL/ml or under the limit of detection per local lab standard) are considered as HBV negative. Subjects should be tested for HIV prior to randomization/enrollment if required by local regulations or institutional review board (IRB)/ethics committee (EC).
- Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of T-DXd. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IMP.
- Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to >Grade 2 for at least 3 months prior to [randomization/enrollment/Cycle 1 Day 1] and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, such as: chemotherapy-induced neuropathy and fatigue.
- Known allergy or hypersensitivity to study treatment or any of the study drug excipients.
- History of severe hypersensitivity reactions to other monoclonal antibodies.
- Pregnant or breastfeeding female patients, or patients who are planning to become pregnant.
- Multiple primary malignancies within 3 years, except for
- adequately resected non-melanoma skin cancer
- curatively treated in-situ disease
- other solid tumors curatively treated
- A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART).
- LVEF< 50% within 28 days before enrolment.
- Prior treatment with an anti-HER2 agent.
- Absence of locally determined HER2 overexpression/amplification on the surgical specimen defined as IHC 0 or 1+ or 2+/ISH not amplified.
- Negativity of ctDNA at the post-operative liquid biopsy.
- 21. Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency based on local laboratory testing before the start of pre-operative FLOT regimen. Confirmation of the assessment of DPD status before the start of pre-operative FLOT in the patient's records should be provided before the enrollment in the interventional study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Milan, 20133
Filippo Pietrantonio, MD, +39 0223903807, filippo.pietrantonio@istitutotumori.mi.it
About this study
Official title: Adjuvant TRastuzumab Deruxtecan Plus Fluoropyrimidine Versus Standard Chemotherapy In HER2-positive Gastric or Gastroesophageal Cancer Patients With Persistence of miNImal Residual Disease in Liquid Biopsy After Pre-operative chemoTherapy and Radical surgerY
TRINITY is designed as a multicentre, randomized, open-label, interventional phase II study aimed at investigating the activity, efficacy and safety of trastuzumab-deruxtecan (T-DXd) plus capecitabine/5-fluorouracil as a post-operative treatment in localized/locally advanced gastric or gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma patients with HER2 overexpression/amplification and positive post-operative ctDNA after pre-operative 5-fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) regimen followed by radical surgery.
Read the detailed description
Patients affected by localized/locally advanced GC/GEJC (Siewert I-II-III)/esophageal adenocarcinoma eligible for peri-operative chemotherapy and radical surgery and deemed fit enough to receive the standard treatment with the triplet FLOT (5-fluorouracil, oxaliplatin and docetaxel) will be evaluated for the enrollment into the observational phase of the study during the standard pre-operative therapeutic management according to the best clinical practice and local guidelines at their Centre.
OBSERVATIONAL PHASE The observational phase will include patients with localized/locally advanced HER2-positive GC/GEJC (Siewert I-II-III)/esophageal adenocarcinoma eligible for standard pre-operative chemotherapy with FLOT for 4 cycles and radical surgery. Patients will undergo an exploratory liquid biopsy (LB) to be centrally collected at baseline, i.e. during the baseline disease staging as per standard clinical practice and prior to the start of the pre-operative FLOT treatment, and a second exploratory LB to be centrally collected at the end of the pre-operative FLOT treatment before the standard surgery. Then, a third mandatory exploratory LB will be collected at 2-6 weeks after surgery and, during the same timepoint, the interventional liquid biopsy will be collected and centrally analyzed with the SignateraTM CE-marked assay as pre-screening test ® in order to determine whether post-operative ctDNA is positive or negative (LB#1: interventional for the potential enrollment in the TRINITY study). Patients will be permitted to be enrolled in the observational phase even after the start of pre-operative FLOT or even after surgery, the lack of availability of one or both pre-surgical exploratory LBs will not preclude the enrolment in the interventional study and postoperative SignateraTM will be offered as prescreening assay.
Patients eligible for the interventional TRINITY study will be those who underwent surgery after the completion of the standard FLOT pre-operative treatment, with locally-confirmed HER2 positive status both on archival pre-treatment tumor biopsy and on post-treatment surgical sample and with detected post-operative ctDNA at LB#1.
In any case of non-eligibility for the interventional study for not fulfilling the molecular pre-screening algorithm, patients will continue the standard treatment as per clinical practice with post-operative FLOT for 4 cycles and standard follow up. In this case, patients with prescreening failure will continue to be followed-up in the frame of the observational phase of the study with the collection of serial LBs at specific timepoints at 3, 6 and 12 months from the date of pre-screening failure (date of results of LB#1), respectively, and then in concomitance with follow-up visits scheduled as per standard clinical practice.
INTERVENTIONAL TRINITY STUDY Patients deemed eligible for the Screening in the interventional TRINITY trial will be screened from 2 and 12 weeks after the date of surgery, in order to start the post-operative treatment no later than 12 weeks after surgery, and will undergo all the screening tests comprising a CT scan including high resolution thorax-abdomen CT scan and echocardiography.
Patients fulfilling all the eligibility criteria for the trial will be randomized according to a 1:1 basis to the experimental treatment with T-DXd at the dose of 6.4 mg/kg intravenous every 3 weeks plus either capecitabine 1000 mg/sqm BID orally on days 1-14 or 5-fluorouracil 600 mg/sqm continuous intravenous infusion on days 1-5, as per Investigator's choice, every 3 weeks for 6 cycles versus the control treatment arm with post-operative FLOT with standard dose and schedule and at the same dose used during the last pre-operative cycle, for 4 cycles.
At 3, 6 and 12 months after randomization, additional exploratory LBs will be collected and at 12 months after randomization also the interventional LB#2 will be collected and centrally analysed to detect ctDNA and to assess the occurrence of ctDNA clearance in both arms as per study primary endpoint.
After randomization, patients will undergo a thorax-abdomen CT scan every 3 months for 1 year to monitor the occurrence of clinical disease relapse. In case of disease relapse before the 12-month post-randomization time-point, the interventional LB#2 will not be performed. After 12 months post-randomization, exploratory LBs will be performed longitudinally during follow-up as per standard clinical practice. Importantly, exploratory LB will be always collected at the time of disease relapse.
This study will pre-screen approximately 600 patients, in order to include about 100 patients in the observational phase and enrol a total number of 46 patients in the interventional study, across 20 Italian Centres in the frame of the GONO network.
- Conditions
- Gastric Cancer, HER2-positive Gastric Cancer
- Being tested
- Experimental, Control
- Keywords
- Trastuzumab-Deruxtecan, Gastric Cancer, HER2-positive Gastric Cancer, Liquid biopsy, Minimal residual disease
- Medical subject headings
- Stomach Neoplasms, Neoplasm, Residual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExperimentalDrug
6 cycles of: T-DXd at the dose of 6.4 mg/kg intravenous every 3 weeks plus capecitabine 1000 mg/sqm BID orally on days 1-14 every 3 weeks or 5-fluorouracil 600 mg/m2/day continuous intravenous infusion on days 1-5 every 3 weeks as per Investigator's choice
ControlDrug
4 cycles of: 5-fluorouracil 2600 mg/m2 continuous intravenous infusion day 1 for 24 hours every 2 weeks, leucovorin 200 mg/m2 intravenous infusion on day 1 every 2 weeks, oxaliplatin 85 mg/m2 intravenous infusion on day 1 every 2 weeks, and docetaxel 50 mg/m2 intravenous infusion on day 1 every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | treatment with T-DXd (6.4 mg/kg intravenous every 3 weeks) plus capecitabine (1000 mg/sqm BID orally on days 1-14 every 3 weeks) or 5-fluorouracil (600 mg/m2/day continuous intravenous infusion on days 1-5 every 3 weeks) as per Investigator's choice for 6 cycles. Receives: Drug: Experimental |
| Control | Active comparator | treatment with post-operative FLOT for 4 cycles as per standard of care and using the doses previously adopted in the last cycle of the preoperative phase, i.e. 5-fluorouracil (2600 mg/m2 continuous intravenous infusion day 1 for 24 hours every 2 weeks), leucovorin (200 mg/m2 intravenous infusion on day 1 every 2 weeks), oxaliplatin 85 mg/m2 (intravenous infusion on day 1 every 2 weeks) and docetaxel (50 mg/m2 intravenous infusion on day 1 every 2 weeks). Receives: Drug: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
ctDNA clearance (negative ctDNA status) at 1 year
The clearance of ctDNA in T-DXd plus capecitabine/5-fluorouracil arm versus standard FLOT continuation at 1 year from randomization.
Measured: 1 year
Secondary outcomes (7)
Disease-free survival
time from the randomization in the study to the occurrence of disease relapse (local and/or distant), second GC/GEJC primary, or death from any cause
Measured: 3 years
Overall survival
time from the randomization in the study to the occurrence of death.
Measured: 3 years
Metastases-free survival
time from the randomization in the study to the first evidence of metastases according to the radiological and clinical assessments detailed in the procedures or death from any cause.
Measured: 3 years
Quality of life - PRO EORTC-QLQ-C30
Quality of life will be assessed through Patient reported outcomes (PRO) instrument. EORTC QLQ-C30 For questions 1-28 of EORTC QLQ-C30 a 4-point scale is used. It scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit")and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome. For the questions 29 and 30 of EORTC QLQ-C30 a 7-points scale is used. It scores from 1 to 7: 1 ("very poor") to 7 ("excellent"). Half points are not allowed. The range is 6. First of all, raw score has to be calculated with mean values. Afterwards linear transformation is performed to be comparable. More points are considered to have a better outcome.
Measured: during adjuvant treatment phase
Quality of life - EORTC QLQ-STO22
Quality of life will be assessed through Patient reported outcomes (PRO) instrument. EORTC QLQ-STO22.
For questions 31-52 of EORTC QLQ-STO22 a 4-point scale is used. It scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome.
Measured: during adjuvant treatment phase
Quality of life - PRO EuroQol EQ-5D-5L
Quality of life will be assessed through Patient reported outcomes (PRO) instrument. EuroQol EQ-5D-5L. The EQ-5D-5L uses for first 5 questions qualitative multiple choice answers with NO SCALE. For the last questions, a score from 0 to 100 indicates from the worst to the best outcome.
Measured: during adjuvant treatment phase
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
incidence of adverse events during the treatment and follow-up phases, assessed according to CTCAE v5.0.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2024
- Study start1 Mar 2024
- Primary completion1 Mar 2027 (estimated)
- Study completion1 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gastric CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gruppo Oncologico del Nord-Ovest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Filippo Pietrantonio, MD, Principal investigator, Fondazione IRCCS - Istituto Nazionale dei Tumori di Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06253650
- Sponsor's protocol ID
- 2023-506662-31-00
- Other IDs
- 2023
- Acronym
- TRINITY
- Status last verified
- Sep 2026
- First submitted
- 2 Feb 2024
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The trial results concerning the primary, secondary and exploratory outcomes will be published according to the standard guidelines. IPD could eventually be requested to the Sponsor and Principal Investigator, who will carefully evaluate the formal and motivated request.
Publications
Nasca V, Bergamo F, Foltran L, Antonuzzo L, Bencardino K, Dell'Aquila E, Corallo S, Spallanzani A, Brunetti O, Spada D, Tamberi S, Cella CA, Avallone A, Fornaro L, Di Donato S, Strippoli A, Puccini A, Tamburini E, Palermo F, Morano F, Pietrantonio F, Raimondi A. Adjuvant TRastuzumab deruxtecan plus fluoropyrimidine versus standard chemotherapy in HER2-positive gastric or gastroesophageal cancer patients with persistence of minimal residual disease in liquid biopsy after pre-operative chemotherapy and radical surgery: the multicentre, phase II randomized TRINITY trial. BMC Cancer. 2025 Apr 8;25(1):633. doi: 10.1186/s12885-025-14063-6.
PubMed 40200187
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjuvant TRastuzumab Deruxtecan Plus Fluoropyrimidine Versus Standard Chemotherapy In HER2-positive Gastric or Gastroesophageal Cancer Patients With Persistence of miNImal Residual Disease in Liquid Biopsy After Pre-operative chemoTherapy and Radical surgerY
- ClinicalTrials.gov ID
- NCT06253650
- Acronym / sponsor ID
- TRINITY / 2023-506662-31-00
- Conditions
- Gastric Cancer, HER2-positive Gastric Cancer
- Keywords
- Trastuzumab-Deruxtecan, Gastric Cancer, HER2-positive Gastric Cancer, Liquid biopsy, Minimal residual disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Gruppo Oncologico del Nord-OvestUniversity, hospital or other
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- 1 Mar 2027 (estimated)
- Study completion
- 1 Mar 2028 (estimated)
- First posted
- 12 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
TRINITY is designed as a multicentre, randomized, open-label, interventional phase II study aimed at investigating the activity, efficacy and safety of trastuzumab-deruxtecan (T-DXd) plus capecitabine/5-fluorouracil as a post-operative treatment in localized/locally advanced gastric or gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma patients with HER2 overexpression/amplification and positive post-operative ctDNA after pre-operative 5-fluorouracil plus leucovorin, oxaliplatin, and docetaxel (FLOT) regimen followed by radical surgery.
Detailed description
Patients affected by localized/locally advanced GC/GEJC (Siewert I-II-III)/esophageal adenocarcinoma eligible for peri-operative chemotherapy and radical surgery and deemed fit enough to receive the standard treatment with the triplet FLOT (5-fluorouracil, oxaliplatin and docetaxel) will be evaluated for the enrollment into the observational phase of the study during the standard pre-operative therapeutic management according to the best clinical practice and local guidelines at their Centre.
OBSERVATIONAL PHASE The observational phase will include patients with localized/locally advanced HER2-positive GC/GEJC (Siewert I-II-III)/esophageal adenocarcinoma eligible for standard pre-operative chemotherapy with FLOT for 4 cycles and radical surgery. Patients will undergo an exploratory liquid biopsy (LB) to be centrally collected at baseline, i.e. during the baseline disease staging as per standard clinical practice and prior to the start of the pre-operative FLOT treatment, and a second exploratory LB to be centrally collected at the end of the pre-operative FLOT treatment before the standard surgery. Then, a third mandatory exploratory LB will be collected at 2-6 weeks after surgery and, during the same timepoint, the interventional liquid biopsy will be collected and centrally analyzed with the SignateraTM CE-marked assay as pre-screening test ® in order to determine whether post-operative ctDNA is positive or negative (LB#1: interventional for the potential enrollment in the TRINITY study). Patients will be permitted to be enrolled in the observational phase even after the start of pre-operative FLOT or even after surgery, the lack of availability of one or both pre-surgical exploratory LBs will not preclude the enrolment in the interventional study and postoperative SignateraTM will be offered as prescreening assay.
Patients eligible for the interventional TRINITY study will be those who underwent surgery after the completion of the standard FLOT pre-operative treatment, with locally-confirmed HER2 positive status both on archival pre-treatment tumor biopsy and on post-treatment surgical sample and with detected post-operative ctDNA at LB#1.
In any case of non-eligibility for the interventional study for not fulfilling the molecular pre-screening algorithm, patients will continue the standard treatment as per clinical practice with post-operative FLOT for 4 cycles and standard follow up. In this case, patients with prescreening failure will continue to be followed-up in the frame of the observational phase of the study with the collection of serial LBs at specific timepoints at 3, 6 and 12 months from the date of pre-screening failure (date of results of LB#1), respectively, and then in concomitance with follow-up visits scheduled as per standard clinical practice.
INTERVENTIONAL TRINITY STUDY Patients deemed eligible for the Screening in the interventional TRINITY trial will be screened from 2 and 12 weeks after the date of surgery, in order to start the post-operative treatment no later than 12 weeks after surgery, and will undergo all the screening tests comprising a CT scan including high resolution thorax-abdomen CT scan and echocardiography.
Patients fulfilling all the eligibility criteria for the trial will be randomized according to a 1:1 basis to the experimental treatment with T-DXd at the dose of 6.4 mg/kg intravenous every 3 weeks plus either capecitabine 1000 mg/sqm BID orally on days 1-14 or 5-fluorouracil 600 mg/sqm continuous intravenous infusion on days 1-5, as per Investigator's choice, every 3 weeks for 6 cycles versus the control treatment arm with post-operative FLOT with standard dose and schedule and at the same dose used during the last pre-operative cycle, for 4 cycles.
At 3, 6 and 12 months after randomization, additional exploratory LBs will be collected and at 12 months after randomization also the interventional LB#2 will be collected and centrally analysed to detect ctDNA and to assess the occurrence of ctDNA clearance in both arms as per study primary endpoint.
After randomization, patients will undergo a thorax-abdomen CT scan every 3 months for 1 year to monitor the occurrence of clinical disease relapse. In case of disease relapse before the 12-month post-randomization time-point, the interventional LB#2 will not be performed. After 12 months post-randomization, exploratory LBs will be performed longitudinally during follow-up as per standard clinical practice. Importantly, exploratory LB will be always collected at the time of disease relapse.
This study will pre-screen approximately 600 patients, in order to include about 100 patients in the observational phase and enrol a total number of 46 patients in the interventional study, across 20 Italian Centres in the frame of the GONO network.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Experimentaltreatment with T-DXd (6.4 mg/kg intravenous every 3 weeks) plus capecitabine (1000 mg/sqm BID orally on days 1-14 every 3 weeks) or 5-fluorouracil (600 mg/m2/day continuous intravenous infusion on days 1-5 every 3 weeks) as per Investigator's choice for 6 cycles. |
| Control | Active comparator | Drug: Controltreatment with post-operative FLOT for 4 cycles as per standard of care and using the doses previously adopted in the last cycle of the preoperative phase, i.e. 5-fluorouracil (2600 mg/m2 continuous intravenous infusion day 1 for 24 hours every 2 weeks), leucovorin (200 mg/m2 intravenous infusion on day 1 every 2 weeks), oxaliplatin 85 mg/m2 (intravenous infusion on day 1 every 2 weeks) and docetaxel (50 mg/m2 intravenous infusion on day 1 every 2 weeks). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Written informed consent and any locally required authorization (such as the European Union [EU] Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
- Compliance with all the study procedures and treatments. Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating Centre.
- Age ≥ 18 years old.
- Eastern Cooperative Oncology group (ECOG) Performance Status 0-1.
- Life expectancy of at least 12 weeks.
Key exclusion criteria (28 listed)
- Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
- Participation in another clinical study with an investigational product during the last 12 months
- Signs of distant metastases at any site.
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, renal disease, neurological disease or peripheral neuropathy, serious chronic gastrointestinal conditions associated with diarrhea, or substance abuse or any other medical or psychiatric illness/social situations that in the opinion of the investigator would limit compliance with study requirement, interfere with the subject's participation in the clinical study, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent or interfere with the evaluation of the clinical study results.
- Patients with a medical history of myocardial infarction (MI) within 6 months before randomization/enrolment, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV), Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Experimental6 cycles of: T-DXd at the dose of 6.4 mg/kg intravenous every 3 weeks plus capecitabine 1000 mg/sqm BID orally on days 1-14 every 3 weeks or 5-fluorouracil 600 mg/m2/day continuous intravenous infusion on days 1-5 every 3 weeks as per Investigator's choice | Drug | Experimental |
| Control4 cycles of: 5-fluorouracil 2600 mg/m2 continuous intravenous infusion day 1 for 24 hours every 2 weeks, leucovorin 200 mg/m2 intravenous infusion on day 1 every 2 weeks, oxaliplatin 85 mg/m2 intravenous infusion on day 1 every 2 weeks, and docetaxel 50 mg/m2 intravenous infusion on day 1 every 2 weeks. | Drug | Control |
Primary outcome
ctDNA clearance (negative ctDNA status) at 1 year
Time frame: 1 year
The clearance of ctDNA in T-DXd plus capecitabine/5-fluorouracil arm versus standard FLOT continuation at 1 year from randomization.
7 secondary outcomes
Disease-free survival
Time frame: 3 years
Overall survival
Time frame: 3 years
Metastases-free survival
Time frame: 3 years
Quality of life - PRO EORTC-QLQ-C30
Time frame: during adjuvant treatment phase
Quality of life - EORTC QLQ-STO22
Time frame: during adjuvant treatment phase
Quality of life - PRO EuroQol EQ-5D-5L
Time frame: during adjuvant treatment phase
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Derived from this study: PubMed 40200187Nasca V, Bergamo F, Foltran L, Antonuzzo L, Bencardino K, Dell'Aquila E, Corallo S, Spallanzani A, Brunetti O, Spada D, Tamberi S, Cella CA, Avallone A, Fornaro L, Di Donato S, Strippoli A, Puccini A, Tamburini E, Palermo F, Morano F, Pietrantonio F, Raimondi A. Adjuvant TRastuzumab deruxtecan plus fluoropyrimidine versus standard chemotherapy in HER2-positive gastric or gastroesophageal cancer patients with persistence of minimal residual disease in liquid biopsy after pre-operative chemotherapy and radical surgery: the multicentre, phase II randomized TRINITY trial. BMC Cancer. 2025 Apr 8;25(1):633. doi: 10.1186/s12885-025-14063-6.
- Individual participant dataSharing planned: No. The trial results concerning the primary, secondary and exploratory outcomes will be published according to the standard guidelines. IPD could eventually be requested to the Sponsor and Principal Investigator, who will carefully evaluate the formal and motivated request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Filippo Pietrantonio, MD principal investigator
Fondazione IRCCS - Istituto Nazionale dei Tumori di Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Experimental in people with Gastric Cancer and HER2-positive Gastric Cancer, run by Gruppo Oncologico del Nord-Ovest at 1 site in Italy.
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 23 inclusion and 28 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 23 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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 Filippo Pietrantonio, MD (+39 0223903807, filippo.pietrantonio@istitutotumori.mi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ctDNA clearance (negative ctDNA status) at 1 year (time frame: 1 year). 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 NCT06253650, which also lists 1 linked publication.
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 23 Sep 2026.