Metastatic Gastric AdenocarcinomaPhase 1/2NCT05927857
Ramucirumab (Cyramza), Nal-IRI (ONIVYDE) and Trifluridine/Tipiracil (Lonsurf) in Second Line Metastatic Gastric Cancer .
A Phase 1/2 study testing nal-IRI /Experimental, Ramucirumab /Experimental and Trifluridine/Tipiracil /Experimental in people with Metastatic Gastric Adenocarcinoma and Second Line, run by National Health Research Institutes, Taiwan at 1 site in Taiwan.
Trial summary
Primary Objectives In phase 1b cohort, to determine MTD (maximum tolerated dose) of nal-IRI (ONIVYDE®) in combination with Ramucirumab (Cyramza®) and TAS-102 (LONSURF®) In phase II cohort, to evaluate disease objective response rate (ORR) of Ramucirumab (Cyramza®), nal-IRI (ONIVYDE®) in combination with TAS-102… Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Metastatic Gastric Adenocarcinoma, Second Line, Chemotherapy
- What is being tested?
- nal-IRI /Experimental, Ramucirumab /Experimental and Trifluridine/Tipiracil /Experimental
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Apr 2024to 31 Dec 2028
- Phase
- Phase 1/2
- 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 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- histologically or cytologically confirmed metastatic gastric adenocarcinoma
- patients have received only first line of systemic therapy, including recurrence during adjuvant therapy or within 6 months after the completion of adjuvant treatment.
- ECOG(Eastern Cooperative Oncology Group) performance status 0 or 1
- patients with HER2/neu-positive tumor must be exposure to Herceptin treatment
- at least one measurable disease according to the RECIST version 1.1;
- patients are aged 20 to 80 years;
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- patients have a life expectancy ≥ 3 months;
- patients have adequate renal function with defined as serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or Ccr ≥ 40 mL/min;
- patients with adequate hepatic function as defined by a total bilirubin ≤1.5 times the ULN, and aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times the ULN or 5 times the ULN in the setting of liver metastases.
- patients have adequate bone marrow function, defined as an absolute neutrophil count ≥ 1500/mm3, hemoglobin ≥9 g/dL, and platelet count ≥ 100,000/mm3 (transfusion or G-CSF support before enrollment is allowed)
- patients have International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) < 1.5 x ULN;
- patients' urinary protein is ≤1+ on dipstick or routine urinalysis or a 24-hour urine collection for protein must demonstrate <1000 mg of protein if urine dipstick or routine analysis is ≥ 2+;
- patients with childbearing potential shall have effective contraception for both the patient and his or her partner during the study;
- female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of protocol therapy;
- the ability to understand and willingness and to sign a written informed consent document.
Who cannot join
- patient can't take oral drugs;
- known hypersensitivity to irinotecan, fluoropyrimidine, or ramucirumab;
- receipt of surgery within the past 4 weeks before study enrollment;
- ≥ grade 2 diarrhea and ascites
- concurrent severe infection with intravenous systemic antibiotics treatment;
- patients have experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy;
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- patients have a prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation;
- patients have:
- cirrhosis at a level of Child-Pugh B (or worse) or
- cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis;
- patients have a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy;
- patients have undergone major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior to the first dose of protocol therapy. Patients have elective or planned major surgery to be performed during the course of the clinical trial;
- patients have uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management;
- patients have experienced any grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy;
- patients have a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy;
- patients are receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted;
- previously received prior nal-IRI (ONIVYDE®) or TAS-102 (LONSURF®) or ramucirumab therapy
- another previous malignancy diagnosed within the past 5 years except for non melanoma skin cancer or stage I cervical cancer;
- pregnant or breast feeding women.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Taiwan1 site, 1 recruiting
- Recruiting
Taipei Veterans General Hospital
Taipei, Taiwan/Taipei
About this study
Official title: A Phase Ib/II Study of Ramucirumab (Cyramza®), Nal-IRI (ONIVYDE®) and Trifluridine/Tipiracil (Lonsurf®) in Second Line Metastatic Gastric Cancer (COOL Study).
Primary Objectives
- In phase 1b cohort, to determine MTD (maximum tolerated dose) of nal-IRI (ONIVYDE®) in combination with Ramucirumab (Cyramza®) and TAS-102 (LONSURF®)
- In phase II cohort, to evaluate disease objective response rate (ORR) of Ramucirumab (Cyramza®), nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®) Secondary Objectives
- To evaluate disease control rate (DCR)
- To evaluate progression-free survival (PFS)
- To evaluate overall survival (OS)
- To assess the safety profile
- To study the blood biomarkers
Read the detailed description
- Eligible patients will be treated with infusional nal-IRI (ONIVYDE®, free form) 50/60/70 mg/m2 over 90 minutes day 1, Ramucirumab 8 mg/kg over 60 minutes day 1, in combination with oral TAS-102 (LONSURF®) 30 mg/m2/b.i.d. day 1-5, every 14 days.
- Every 14 days count as one cycle.
- Patients will be treated until disease progression, unacceptable toxicity or other condition meeting the off-study criteria.
- Scheme of phase 1b: dose Level 0 to 2 will be tested with the following dose levels:
- Dose level 0= Ramucirumab(Cyramza®) 8mg/kg on day 1, nal-IRI (ONIVYDE®, free form) 50 mg/m2 on day 1 plus Trifluridine/Tipiracil (Lonsurf®) 30mg/m2 on day 1-5, q2wk
- Dose level 1= Ramucirumab(Cyramza®) 8mg/kg on day 1, nal-IRI (ONIVYDE®, free form) 60 mg/m2 on day 1 plus Trifluridine/Tipiracil (Lonsurf®) 30mg/m2 on day 1-5, q2wk
- Dose level 2= Ramucirumab(Cyramza®) 8mg/kg on day 1, nal-IRI (ONIVYDE®, free form) 70 mg/m2 on day 1 plus Trifluridine/Tipiracil (Lonsurf®) 30mg/m2 on day 1-5, q2wk
- Adaptive phase IB cohort:
- 3+3 dose escalation will be applied for phase Ib cohort. All treated patients of MTD dose level in phase 1b cohort will be incorporated into phase II cohort for final analysis. No intra-patient dose escalation is allowed during DLT period. Patients could only have dose modification after the DLT period. G-CSF prophylaxis is not allowed in DLT period.
- Dose escalation rule: Two to six patients will be enrolled in each cohort depending on cases with DLTs. The starting dose is dose level 0. If none of the first 3 patients experiences DLT, then dose escalation will proceed to the next cohort of patients. If only 1 of 3 patients developed DLT, the cohort will be expanded to 6 patients. If more than 1 patient developed DLT at a certain dose level/group, the dose level/group is considered intolerable to the patients. If no more than 1 out of 6 patients experience DLT, the dose level/group is considered tolerable. A minimum of 6 evaluable patients will be treated at the MTD. The MTD at which no more than 1 of the 6 patients experience DLT will be determined for the phase II cohort. Based on results from phase IB cohort, MTD will be determined. All treated population in MTD cohort will be incorporated into phase II cohort for final analysis.
- Conditions
- Metastatic Gastric Adenocarcinoma, Second Line, Chemotherapy
- Being tested
- nal-IRI /Experimental, Ramucirumab /Experimental, Trifluridine/Tipiracil /Experimental
- Keywords
- nal-IRI (ONIVYDE), TAS-102 (LONSURF), Ramucirumab (Cyramza)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nal-IRI /ExperimentalDrug
Also called ONIVYDE
infusional 50/60/70 mg/m2 over 90 minutes day 1, every 14 days.
Ramucirumab /ExperimentalDrug
Also called Cyramza
infusional 8mg/kg over 60 minutes day 1, every 14 days.
Trifluridine/Tipiracil /ExperimentalDrug
Also called LONSURF
oral 30 mg/m2/b.i.d. day 1-5, every 14 days.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b/II | Experimental | * Infusional nal-IRI (ONIVYDE, free form) 50/60/70 mg/m2 over 90 minutes day 1.
* Infusional Ramucirumab(Cyramza)8 mg/kg over 60 minutes day 1.
* oral Trifluridine/Tipiracil TAS-102 (LONSURF) 30 mg/m2/b.i.d. day 1-5.
* Every 14 days count as one cycle. Receives: Drug: nal-IRI /Experimental; Drug: Ramucirumab /Experimental; Drug: Trifluridine/Tipiracil /Experimental |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine MTD (maximum tolerated dose) of nal-IRI (ONIVYDE)
All treated patients of MTD dose level in phase 1b cohort will be incorporated into phase II cohort for final analysis.
Measured: Phase I last patient in has been treated for 28 days.
To evaluate disease objective response rate (ORR)
Based on results from phase Ib cohort, MTD will be determined. All treated population in MTD cohort will be incorporated into phase II cohort for final analysis.
Measured: Whichever occurs first assessed up to 24 months.
Secondary outcomes (5)
•To evaluate disease control rate (DCR)
•Patients will be treated until disease progression, unacceptable toxicity or other condition meeting the off-study criteria.
Measured: The time from registration to death from any cause assessed up to 24 months.
•To evaluate progression-free survival (PFS)
- objective tumor response according to RECIST v1.1 guidelines.
Measured: The time from registration to occurrence of progression based on the tumor response assessment by scheduled or un- scheduled CT scan or MRI. (whichever occurs first assessed up to 24 months)
•To evaluate overall survival (OS)
the time from the date of first study treatment to the date of patient death, due to any cause, or to the last date the patient was known to be alive.
Measured: The time from registration to death from any cause assessed up to 24 months.
•To assess the safety profile
•Safety evaluations: physical examination, vital signs, body weight, ECOG performance status, clinical laboratory values (biochemistry, hematology, and urinalysis), and any adverse event (AE) graded by using CTCAE v5.0 if applicable.
Measured: The time from registration to death from every 14 days assessed up to 24 months.
•To study the blood biomarkers
- To evaluate the drug sensitivity of circulating tumor cells to, including but not limited to irinotecan, fluorouracil and ramucirumab.
- Patients enrolled in both phase Ib and phase II parts will participate in biomarker study
Measured: The time from baseline on day 1.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2023
- Study start1 Apr 2024
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Metastatic Gastric AdenocarcinomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Health Research Institutes, Taiwan
- Sponsor type
- University, hospital or other
- Collaborators
- Taipei Veterans General Hospital, Taiwan, China Medical University Hospital, National Cheng-Kung University Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital, Chang Gung Memorial Hospital
- Responsible party
- Sponsor
- Investigators
- Nai-Jung Chiang, MD-PhD, Principal investigator, National Health Research Institutes, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05927857
- Sponsor's protocol ID
- T1223
- Status last verified
- Apr 2026
- First submitted
- 14 Jun 2023
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Innocenti F, Kroetz DL, Schuetz E, Dolan ME, Ramirez J, Relling M, Chen P, Das S, Rosner GL, Ratain MJ. Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics. J Clin Oncol. 2009 Jun 1;27(16):2604-14. doi: 10.1200/JCO.2008.20.6300. Epub 2009 Apr 6.
PubMed 19349540Mathijssen RH, van Alphen RJ, Verweij J, Loos WJ, Nooter K, Stoter G, Sparreboom A. Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res. 2001 Aug;7(8):2182-94.
PubMed 11489791Smith NF, Figg WD, Sparreboom A. Pharmacogenetics of irinotecan metabolism and transport: an update. Toxicol In Vitro. 2006 Mar;20(2):163-75. doi: 10.1016/j.tiv.2005.06.045. Epub 2005 Nov 3.
PubMed 16271446Kawato Y, Aonuma M, Hirota Y, Kuga H, Sato K. Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res. 1991 Aug 15;51(16):4187-91.
PubMed 1651156Garcia-Carbonero R, Supko JG. Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins. Clin Cancer Res. 2002 Mar;8(3):641-61.
PubMed 11895891Vanhoefer U, Harstrick A, Achterrath W, Cao S, Seeber S, Rustum YM. Irinotecan in the treatment of colorectal cancer: clinical overview. J Clin Oncol. 2001 Mar 1;19(5):1501-18. doi: 10.1200/JCO.2001.19.5.1501.
PubMed 11230497Lee DH, Kim HT, Han JY, Lee SY, Yoon SJ, Kim HY, Lee JS. A phase II trial of modified weekly irinotecan and cisplatin for chemotherapy-naive patients with metastatic or recurrent squamous cell carcinoma of the esophagus. Cancer Chemother Pharmacol. 2008 Jan;61(1):83-8. doi: 10.1007/s00280-007-0450-7. Epub 2007 Apr 28.
PubMed 17468871Chen SC, Chang PM, Yang MH. Cisplatin/Tegafur/Uracil/Irinotecan Triple Combination Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase I/II Clinical Study. Oncologist. 2016 May;21(5):537-8. doi: 10.1634/theoncologist.2015-0515. Epub 2016 Apr 18.
PubMed 27091418Tsai CS, Park JW, Chen LT. Nanovector-based therapies in advanced pancreatic cancer. J Gastrointest Oncol. 2011 Sep;2(3):185-94. doi: 10.3978/j.issn.2078-6891.2011.034.
PubMed 22811849Chang TC, Shiah HS, Yang CH, Yeh KH, Cheng AL, Shen BN, Wang YW, Yeh CG, Chiang NJ, Chang JY, Chen LT. Phase I study of nanoliposomal irinotecan (PEP02) in advanced solid tumor patients. Cancer Chemother Pharmacol. 2015 Mar;75(3):579-86. doi: 10.1007/s00280-014-2671-x. Epub 2015 Jan 11.
PubMed 25577133Chiang NJ, Chao TY, Hsieh RK, Wang CH, Wang YW, Yeh CG, Chen LT. A phase I dose-escalation study of PEP02 (irinotecan liposome injection) in combination with 5-fluorouracil and leucovorin in advanced solid tumors. BMC Cancer. 2016 Nov 21;16(1):907. doi: 10.1186/s12885-016-2933-6.
PubMed 27871319Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. doi: 10.1093/annonc/mdt002. Epub 2013 Feb 13.
PubMed 23406728Ko AH, Tempero MA, Shan YS, Su WC, Lin YL, Dito E, Ong A, Wang YW, Yeh CG, Chen LT. A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer. Br J Cancer. 2013 Aug 20;109(4):920-5. doi: 10.1038/bjc.2013.408. Epub 2013 Jul 23.
PubMed 23880820Wang-Gillam A, Li CP, Bodoky G, Dean A, Shan YS, Jameson G, Macarulla T, Lee KH, Cunningham D, Blanc JF, Hubner RA, Chiu CF, Schwartsmann G, Siveke JT, Braiteh F, Moyo V, Belanger B, Dhindsa N, Bayever E, Von Hoff DD, Chen LT; NAPOLI-1 Study Group. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545-557. doi: 10.1016/S0140-6736(15)00986-1. Epub 2015 Nov 29.
PubMed 26615328Chiang NJ, Bai LY, Ho IW, Hsu CH, Liang YH, Chiu CF, Lin CC, Chang KY, Chen SH, Tsai HJ, Lin YP, Chen LT, Lin CC. A phase I study of liposomal Irinotecan (ONIVYDE(R)) in combination with TAS-102 (LONSURF(R)) in refractory solid tumors. Invest New Drugs. 2025 Jun;43(3):709-718. doi: 10.1007/s10637-025-01547-2. Epub 2025 Jun 4.
PubMed 40468090
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of Ramucirumab (Cyramza®), Nal-IRI (ONIVYDE®) and Trifluridine/Tipiracil (Lonsurf®) in Second Line Metastatic Gastric Cancer (COOL Study).
- ClinicalTrials.gov ID
- NCT05927857
- Acronym / sponsor ID
- T1223
- Conditions
- Metastatic Gastric Adenocarcinoma, Second Line, Chemotherapy
- Keywords
- nal-IRI (ONIVYDE), TAS-102 (LONSURF), Ramucirumab (Cyramza)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- National Health Research Institutes, TaiwanUniversity, hospital or other
- Collaborators
- Taipei Veterans General Hospital, Taiwan, China Medical University Hospital, National Cheng-Kung University Hospital, Kaohsiung Medical University Chung-Ho Memorial Hospital, Chang Gung Memorial Hospital
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 3 Jul 2023 (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.
Primary Objectives
- In phase 1b cohort, to determine MTD (maximum tolerated dose) of nal-IRI (ONIVYDE®) in combination with Ramucirumab (Cyramza®) and TAS-102 (LONSURF®)
- In phase II cohort, to evaluate disease objective response rate (ORR) of Ramucirumab (Cyramza®), nal-IRI (ONIVYDE®) in combination with TAS-102 (LONSURF®) Secondary Objectives
- To evaluate disease control rate (DCR)
- To evaluate progression-free survival (PFS)
- To evaluate overall survival (OS)
- To assess the safety profile
- To study the blood biomarkers
Detailed description
- Eligible patients will be treated with infusional nal-IRI (ONIVYDE®, free form) 50/60/70 mg/m2 over 90 minutes day 1, Ramucirumab 8 mg/kg over 60 minutes day 1, in combination with oral TAS-102 (LONSURF®) 30 mg/m2/b.i.d. day 1-5, every 14 days.
- Every 14 days count as one cycle.
- Patients will be treated until disease progression, unacceptable toxicity or other condition meeting the off-study criteria.
- Scheme of phase 1b: dose Level 0 to 2 will be tested with the following dose levels:
- Dose level 0= Ramucirumab(Cyramza®) 8mg/kg on day 1, nal-IRI (ONIVYDE®, free form) 50 mg/m2 on day 1 plus Trifluridine/Tipiracil (Lonsurf®) 30mg/m2 on day 1-5, q2wk
- Dose level 1= Ramucirumab(Cyramza®) 8mg/kg on day 1, nal-IRI (ONIVYDE®, free form) 60 mg/m2 on day 1 plus Trifluridine/Tipiracil (Lonsurf®) 30mg/m2 on day 1-5, q2wk
- Dose level 2= Ramucirumab(Cyramza®) 8mg/kg on day 1, nal-IRI (ONIVYDE®, free form) 70 mg/m2 on day 1 plus Trifluridine/Tipiracil (Lonsurf®) 30mg/m2 on day 1-5, q2wk
- Adaptive phase IB cohort:
- 3+3 dose escalation will be applied for phase Ib cohort. All treated patients of MTD dose level in phase 1b cohort will be incorporated into phase II cohort for final analysis. No intra-patient dose escalation is allowed during DLT period. Patients could only have dose modification after the DLT period. G-CSF prophylaxis is not allowed in DLT period.
- Dose escalation rule: Two to six patients will be enrolled in each cohort depending on cases with DLTs. The starting dose is dose level 0. If none of the first 3 patients experiences DLT, then dose escalation will proceed to the next cohort of patients. If only 1 of 3 patients developed DLT, the cohort will be expanded to 6 patients. If more than 1 patient developed DLT at a certain dose level/group, the dose level/group is considered intolerable to the patients. If no more than 1 out of 6 patients experience DLT, the dose level/group is considered tolerable. A minimum of 6 evaluable patients will be treated at the MTD. The MTD at which no more than 1 of the 6 patients experience DLT will be determined for the phase II cohort. Based on results from phase IB cohort, MTD will be determined. All treated population in MTD cohort will be incorporated into phase II cohort for final analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phase 1b/II | Experimental | Drug: nal-IRI /Experimental, Drug: Ramucirumab /Experimental, Drug: Trifluridine/Tipiracil /Experimental* Infusional nal-IRI (ONIVYDE, free form) 50/60/70 mg/m2 over 90 minutes day 1. * Infusional Ramucirumab(Cyramza)8 mg/kg over 60 minutes day 1. * oral Trifluridine/Tipiracil TAS-102 (LONSURF) 30 mg/m2/b.i.d. day 1-5. * Every 14 days count as one cycle. |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- histologically or cytologically confirmed metastatic gastric adenocarcinoma
- patients have received only first line of systemic therapy, including recurrence during adjuvant therapy or within 6 months after the completion of adjuvant treatment.
- ECOG(Eastern Cooperative Oncology Group) performance status 0 or 1
- patients with HER2/neu-positive tumor must be exposure to Herceptin treatment
- at least one measurable disease according to the RECIST version 1.1;
Key exclusion criteria (19 listed)
- patient can't take oral drugs;
- known hypersensitivity to irinotecan, fluoropyrimidine, or ramucirumab;
- receipt of surgery within the past 4 weeks before study enrollment;
- ≥ grade 2 diarrhea and ascites
- concurrent severe infection with intravenous systemic antibiotics treatment;
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 |
|---|---|---|
| nal-IRI /ExperimentalAlso: ONIVYDEinfusional 50/60/70 mg/m2 over 90 minutes day 1, every 14 days. | Drug | Phase 1b/II |
| Ramucirumab /ExperimentalAlso: Cyramzainfusional 8mg/kg over 60 minutes day 1, every 14 days. | Drug | Phase 1b/II |
| Trifluridine/Tipiracil /ExperimentalAlso: LONSURForal 30 mg/m2/b.i.d. day 1-5, every 14 days. | Drug | Phase 1b/II |
Primary outcome
To determine MTD (maximum tolerated dose) of nal-IRI (ONIVYDE)
Time frame: Phase I last patient in has been treated for 28 days.
All treated patients of MTD dose level in phase 1b cohort will be incorporated into phase II cohort for final analysis.
To evaluate disease objective response rate (ORR)
Time frame: Whichever occurs first assessed up to 24 months.
Based on results from phase Ib cohort, MTD will be determined. All treated population in MTD cohort will be incorporated into phase II cohort for final analysis.
5 secondary outcomes
•To evaluate disease control rate (DCR)
Time frame: The time from registration to death from any cause assessed up to 24 months.
•To evaluate progression-free survival (PFS)
Time frame: The time from registration to occurrence of progression based on the tumor response assessment by scheduled or un- scheduled CT scan or MRI. (whichever occurs first assessed up to 24 months)
•To evaluate overall survival (OS)
Time frame: The time from registration to death from any cause assessed up to 24 months.
•To assess the safety profile
Time frame: The time from registration to death from every 14 days assessed up to 24 months.
•To study the blood biomarkers
Time frame: The time from baseline on day 1.
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 9 Apr 2026.
- Results publication: PubMed 19349540Innocenti F, Kroetz DL, Schuetz E, Dolan ME, Ramirez J, Relling M, Chen P, Das S, Rosner GL, Ratain MJ. Comprehensive pharmacogenetic analysis of irinotecan neutropenia and pharmacokinetics. J Clin Oncol. 2009 Jun 1;27(16):2604-14. doi: 10.1200/JCO.2008.20.6300. Epub 2009 Apr 6.
- Results publication: PubMed 11489791Mathijssen RH, van Alphen RJ, Verweij J, Loos WJ, Nooter K, Stoter G, Sparreboom A. Clinical pharmacokinetics and metabolism of irinotecan (CPT-11). Clin Cancer Res. 2001 Aug;7(8):2182-94.
- Results publication: PubMed 16271446Smith NF, Figg WD, Sparreboom A. Pharmacogenetics of irinotecan metabolism and transport: an update. Toxicol In Vitro. 2006 Mar;20(2):163-75. doi: 10.1016/j.tiv.2005.06.045. Epub 2005 Nov 3.
- Results publication: PubMed 1651156Kawato Y, Aonuma M, Hirota Y, Kuga H, Sato K. Intracellular roles of SN-38, a metabolite of the camptothecin derivative CPT-11, in the antitumor effect of CPT-11. Cancer Res. 1991 Aug 15;51(16):4187-91.
- Results publication: PubMed 11895891Garcia-Carbonero R, Supko JG. Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins. Clin Cancer Res. 2002 Mar;8(3):641-61.
- Results publication: PubMed 11230497Vanhoefer U, Harstrick A, Achterrath W, Cao S, Seeber S, Rustum YM. Irinotecan in the treatment of colorectal cancer: clinical overview. J Clin Oncol. 2001 Mar 1;19(5):1501-18. doi: 10.1200/JCO.2001.19.5.1501.
- Results publication: PubMed 17468871Lee DH, Kim HT, Han JY, Lee SY, Yoon SJ, Kim HY, Lee JS. A phase II trial of modified weekly irinotecan and cisplatin for chemotherapy-naive patients with metastatic or recurrent squamous cell carcinoma of the esophagus. Cancer Chemother Pharmacol. 2008 Jan;61(1):83-8. doi: 10.1007/s00280-007-0450-7. Epub 2007 Apr 28.
- Results publication: PubMed 27091418Chen SC, Chang PM, Yang MH. Cisplatin/Tegafur/Uracil/Irinotecan Triple Combination Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: A Phase I/II Clinical Study. Oncologist. 2016 May;21(5):537-8. doi: 10.1634/theoncologist.2015-0515. Epub 2016 Apr 18.
- Results publication: PubMed 22811849Tsai CS, Park JW, Chen LT. Nanovector-based therapies in advanced pancreatic cancer. J Gastrointest Oncol. 2011 Sep;2(3):185-94. doi: 10.3978/j.issn.2078-6891.2011.034.
- Results publication: PubMed 25577133Chang TC, Shiah HS, Yang CH, Yeh KH, Cheng AL, Shen BN, Wang YW, Yeh CG, Chiang NJ, Chang JY, Chen LT. Phase I study of nanoliposomal irinotecan (PEP02) in advanced solid tumor patients. Cancer Chemother Pharmacol. 2015 Mar;75(3):579-86. doi: 10.1007/s00280-014-2671-x. Epub 2015 Jan 11.
- Results publication: PubMed 27871319Chiang NJ, Chao TY, Hsieh RK, Wang CH, Wang YW, Yeh CG, Chen LT. A phase I dose-escalation study of PEP02 (irinotecan liposome injection) in combination with 5-fluorouracil and leucovorin in advanced solid tumors. BMC Cancer. 2016 Nov 21;16(1):907. doi: 10.1186/s12885-016-2933-6.
- Results publication: PubMed 23406728Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. doi: 10.1093/annonc/mdt002. Epub 2013 Feb 13.
- Individual participant dataSharing planned: No
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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.
Nai-Jung Chiang, MD-PhD principal investigator
National Health Research Institutes, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing nal-IRI /Experimental, Ramucirumab /Experimental and Trifluridine/Tipiracil /Experimental in people with Metastatic Gastric Adenocarcinoma and Second Line, run by National Health Research Institutes, Taiwan at 1 site in Taiwan.
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 15 inclusion and 19 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 9 Apr 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 Taiwan. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Chien-Ya Hung, BS (+886-3-7206166 ext. 35104, 951106@nhri.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine MTD (maximum tolerated dose) of nal-IRI (ONIVYDE) (time frame: Phase I last patient in has been treated for 28 days.). The study lists 2 primary outcomes in all. 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 NCT05927857, which also lists 15 linked publications.
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 9 Apr 2026.