A multicenter study to evaluate the safety and efficacy of T-DXd in combination with ramucirumab in patients with HER2 low mutations gastric or gastroesophageal junction (GEJ) adenocarcinoma
- Conditions
- Neoplasms
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 58
1. Able and willing to give written informed consent and has signed the appropriate written informed consent form(ICF) prior to performance of any trial activities.
2. Eligible male and female subjects aged =19 years.
3. Histologically or cytologically proven metastatic or locally advanced HER2 low gastric or GEJ adenocarcinoma: The definition of HER2 low is 1+ by immunohistochemistry (IHC) or 2+ by IHC and without HER2 gene amplification (negative by in situ hybridization[ISH]).
4. Progressed after 1st line palliative treatment. Adjuvant chemotherapy will be counted as 1st line treatment if the cancer has recurred within 6 months of completion of adjuvant chemotherapy.
5. Has measurable or evaluable disease as determined by RECIST ver 1.1.
6. ECOG performance status of 0 -1 at trial entry.
7. Life expectancy =12 weeks as judged by the Investigator.
8. Has LVEF = 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before enrollment
9. Adequate organ and bone marrow function within 14 days before enrollment as described below. All parameters must meet the inclusion criteria on the same day, and must be the most recent results available (hematology and chemistry can be done on separate days if within the window).
10. Adequate treatment washout period before randomization/enrollment, defined in Table 2 below
11. 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 within 7 days prior to first dose of protocol therapy and urine beta-human chorionic gonadotropin (ß-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.
12. 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.
13. 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 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
1. Anticancer treatment within 14 days before the start of trial treatment, e.g., cytoreductive therapy, radiotherapy (with the exception of palliative bone-directed radiotherapy), immune therapy, or cytokine therapy.
2. Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy), or the patient has elective of planned major surgery to be performed during the course of the clinical trial
3. Have received more than 2 prior lines of chemotherapy (However, if adjuvant chemotherapy is performed after surgery and recurrence within 6 months after completion, adjuvant chemotherapy is considered the first-line chemotherapy)
4. Grade = 2 peripheral neuropathy delete
5. Multiple primary malignancies within 3 years, with the exception of
• adequately resected non-melanoma skin cancer
• curatively treated in-situ disease
• other solid tumors curatively treated
6. Participants with a medical history of myocardial infarction within 6 months before treatment, 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), and without any myocardial-related symptoms, should have a cardiologic consultation before enrollment to rule out myocardial infarction.
7. Corrected QT interval (QTcF) prolongation to > 470 msec (females) or >450 msec (males) based on an average of the screening triplicate 12-lead ECG.
8. Gastrointestinal perforation or fistula or any Grade 3-4 bleeding within 3 months of first dose of protocol therapy; or any arterial thromboembolic event, significant gastro-intestinal bleeding or any significant venous thromboembolism within 3 months before treatment (venous port or catheter thrombosis or superficial venous thrombosis are not considered significant”).
9. 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.
10. Lung criteria:
A. 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.)
B. 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.
C. Prior pneumonectomy (complete)
11. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to the first dose of study treatment.
12. Has substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions that may, in the opinion of the investigator, interfere with the
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Ib - recommended Phase 2 dose (RP2D); II - progression free survival (PFS) rate at 24 weeks
- Secondary Outcome Measures
Name Time Method safety