BridgeMD
New treatment option for Stomach Neoplasm
Official title Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer
ClinicalTrials.gov ID: NCT06085755
What this study is testing
What is Trastuzumab deruxtecan?
Trastuzumab deruxtecan is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for stomach neoplasm.
Also referred to as T-DXd.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- Despite recent advances, the prognosis of patients with advanced gastric cancer remains poor. At present, regimens that combine a platinum and fluorouracil agent either alone or in combination with a third drug such as epirubicin or taxane constitute the most effective treatment option in the first-line metastatic setting, resulting in a median OS of approximately 10 months.
- Phase 2: a mid-size study of how well it works
- You might receive a placebo (an inactive treatment) instead of the study drug.
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 19 and older
You may be able to join if
- Provision of fully informed consent prior to any study specific procedures.
- Patients must be ≥ 19 years of age
- Has a pathologically documented advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction with at least one measurable lesion...
- HER2-low (HER2 1+, HER2 2+ (SISH negative))
- Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and...
You likely can't join if
- Medical history of myocardial infarction within 6 months before registration, symptomatic congestive heart failure (CHF) (New York Heart Association...
- History of (non-infectious) ILD / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled...
- Has a pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion...
- Has uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
- Active hepatitis B or C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1. people with past or...
- Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control...
See the full eligibility criteria
Who can join
- Provision of fully informed consent prior to any study specific procedures.
- Patients must be ≥ 19 years of age
- Has a pathologically documented advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction with at least one measurable lesion according to the modified RECIST 1.1 are eligible
- HER2-low (HER2 1+, HER2 2+ (SISH negative))
- Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
- ECOG performance status 0-1 with no deterioration between screening and the first dose of study treatment.
- Patients must have a life expectancy ≥ 3 months from proposed first dose date.
- Patients must have had a washout period of 2 weeks for any prior therapy prior to the start of study drug. The following intervals between the end of the prior treatment and first dose of study drug must be observed:
- Major surgery ≥ 4 weeks
- Radiation Therapy including palliative stereotactic radiation therapy to chest ≥ 4 weeks
- Palliative stereotactic radiation therapy to other anatomic areas including whole brain radiation ≥ 2 weeks
- Anti-Cancer chemotherapy [Immunotherapy (non-antibody based therapy)], retinoid therapy, hormonal therapy ≥ 3 weeks
- Antibody based anti-cancer therapy ≥ 4 weeks
- Targeted agents and small molecules ≥ 2 weeks or 5 half-lives, whichever is longer
- Nitrosoureas or mitomycin C ≥ 6 weeks
- TKIs approved for treatment of NSCLC ≥1 week (baseline CT scan must be completed after discontinuation of TKI
- Chloroquine/Hydroxychloroquine ≥ 14 days
- Cell-free and CART, peritoneal shunt or drainage of pleural effusion, ascites or pericardial effusion ≥ 2 weeks prior to screening assessment
- Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below:
- Hemoglobin ≥8.0 g/dL (Red blood cell transfusion is not allowed within 1 week prior to the day)
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (G-CSF administration is not allowed within 2 weeks prior to the day)
- Platelet count ≥100 x 109/L (Platelet transfusion is not allowed within 1 week prior to the day)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) or \< 3×ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline
- AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case it must be ≤ 5x ULN
- Serum creatinine ≤1.5 x institutional ULN
- CrCl 30≥mL/min as determined by Cockcroft Gault (using actual body weight)
- Serum albumin ≥ 2.5 g/dL
- International normalised ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN
- Female patients must be using a highly effective method of contraception (refer to the restrictions on P37) during the clinical trial and for 7 months after permanent discontinuation of the study drug. There must be...
- Post-menopausal women defined as aged more than 50 years and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatment.
- Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not tubal ligation.
- Amenorrhoeic for 12 months and serum follicle-stimulating hormone (FSH), lutenizing hormone (LH) and plasma oestradiol levels in the postmenopausal range for the institution More detailed information is provided in...
- 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. Complete heterosexual...
- Mandatory biopsy during the screening window prior to dosing and at progression
What rules you out
- Medical history of myocardial infarction within 6 months before registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV, Section 17.4), troponin levels consistent with...
- 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.
- Has a pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). (Drainage and CART are not allowed within 2 weeks prior...
- Has uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
- Active hepatitis B or C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1. people with past or resolved hepatitis B virus (HBV) infection who are anti-HBc positive (+)...
- Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. people with treated brain metastases that are no longer...
- Has clinically significant corneal disease in the opinion of the investigator.
- Prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than chronic toxicities...
- Chemotherapy-induced neuropathy
- Fatigue
- Residual toxicities from prior IO treatment: Grade 1 or Grade 2 endocrinopathies which may include:
- Hypothyroidism/hyperthyroidism
- Type 1 diabetes
- Hyperglycaemia
- Adrenal insufficiency
- Adrenalitis
- Skin hypopigmentation (vitiligo)
- Any gastrointestinal condition that would preclude adequate absorption of afatinib including but not limited to inability to swallow oral medication, refractory nausea and vomiting, chronic gastrointestinal diseases or...
- Active or prior documented autoimmune or inflammatory disorders (including IBD [e.g. Chohn's disease, ulcerative colitis or diverticulitis], SLE, sarcoidosis syndrome, tuberculosis, Wegener syndrome, myasthenia gravis...
- people with vitiligo or alopecia, hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment; patients with coeliac disease controlled by diet alone and...
- HbsAg carrier without active viral infection and under entecavir prophylaxis will be allowed.
- Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and...
- Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression. Note: people previously treated for CNS metastases that are asymptomatic, radiographically and neurologically...
- Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for ≤3...
- Patient was in receipt of any live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study therapy.
- Patients currently receiving (or unable to stop use at least 2 weeks) prior to receiving the first dose of afatinib, medications known to be potent inhibitors of CYP1A2 or strong inducers of CYP3A4 with a narrow...
- Patient with any of the following cardiac criteria:
- Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from electrogram (ECG) using Friderecia's correction
- Any clinicallly important abnormalities in rhythm, conduction or morphology of resting ECG e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR Interval \>250 msec.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, uncorrectable chronic hypokalaemia, congenital long QT syndrome, family history (first-degree relatives) of long...
- Uncontrolled hypotension: systolic BP \ 20 mmHg
- Atrial fibrillation with a ventricular rate \>100 bpm on ECG at rest
- Symptomatic heart failure (NYHA grade II-IV)
- Known reduced LVEF \< 55%
- Prior or current cardiomyopathy
- Prior or current acute myocardial infarction
- Severe valvular heart disease
- Uncontrolled angina (Canadian Cardiovascular Society grade II-IV despite medical therapy)
- Stroke or transient ischaemic attack in prior to screening
- Acute coronary syndrome within 6 months prior to starting treatment
- Any evidence of severe or uncontrolled systemic disease, including active infection (requiring antibiotics, antifungals or antivirals), diabetes type I and II, uncontrolled seizures, bleeding diatheses, severe COPD...
- Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of...
- Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial...
- History of active primary immunodeficiency
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 7 months after the last dose of Trastuzumab...
- Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
- History of allogenic organ transplantation.
- 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...
- 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...
- Prior pneumonectomy (complete)
The study team makes the final eligibility decision.
Where it's taking place
- Seoul, South Korea
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 19 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Seoul, South Korea. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.