A Phase Ib/II Study of Ramucirumab (Cyramza®), Nal-IRI (ONIVYDE®) and Trifluridine/Tipiracil (Lonsurf®) in Second Line Metastatic Gastric Cancer (COOL Study).

Trial ID: NCT05927857

Interventional - Phase 1/2 - Recruiting

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

Conditions

• Metastatic Gastric Adenocarcinoma
• Second Line
• Chemotherapy

Interventions

• nal-IRI /Experimental
• Ramucirumab /Experimental
• Trifluridine/Tipiracil /Experimental

Eligibility

Inclusion criteria

• 1. histologically or cytologically confirmed metastatic gastric adenocarcinoma
• 2. patients have received only first line of systemic therapy, including recurrence during adjuvant therapy or within 6 months after the completion of adjuvant treatment.
• 3. ECOG(Eastern Cooperative Oncology Group) performance status 0 or 1
• 4. patients with HER2/neu-positive tumor must be exposure to Herceptin treatment
• 5. at least one measurable disease according to the RECIST version 1.1;
• 6. patients are aged 20 to 80 years;
• 7. patients have a life expectancy ≥ 3 months;
• 8. patients have adequate renal function with defined as serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or Ccr ≥ 40 mL/min;
• 9. 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.
• 10. 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)
• 11. patients have International Normalized Ratio (INR) ≤1.5 and a partial thromboplastin time (PTT) (PTT/aPTT) \< 1.5 x ULN;
• 12. 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+;
• 13. patients with childbearing potential shall have effective contraception for both the patient and his or her partner during the study;
• 14. female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of protocol therapy;
• 15. the ability to understand and willingness and to sign a written informed consent document.

Exclusion criteria

• 1. patient can't take oral drugs;
• 2. known hypersensitivity to irinotecan, fluoropyrimidine, or ramucirumab;
• 3. receipt of surgery within the past 4 weeks before study enrollment;
• 4. ≥ grade 2 diarrhea and ascites
• 5. concurrent severe infection with intravenous systemic antibiotics treatment;
• 6. 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;
• 7. patients have a prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation;
• 8. 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;
• 9. patients have a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy;
• 10. 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;
• 11. patients have uncontrolled or poorly-controlled hypertension (\>160 mmHg systolic or \> 100 mmHg diastolic for \>4 weeks) despite standard medical management;
• 12. patients have experienced any grade 3-4 GI bleeding within 3 months prior to first dose of protocol therapy;
• 13. 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;
• 14. patients are receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted;
• 15. previously received prior nal-IRI (ONIVYDE®) or TAS-102 (LONSURF®) or ramucirumab therapy
• 16. another previous malignancy diagnosed within the past 5 years except for non melanoma skin cancer or stage I cervical cancer;
• 17. pregnant or breast feeding women.

Sponsor

National Health Research Institutes, Taiwan, 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

Source: ClinicalTrials.gov

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