Liposomal Irinotecan Plus Cisplatin in Patients With Advanced or Metastatic Solid Malignancies

Inclusion Criteria:

* 1\. Patients with age 20-85 years old.
* 2\. Cytologically or histologically confirmed solid malignancies which are locally advanced, recurrent or metastatic diseases. The disease cannot be cured by surgical intervention or local therapies.
* 3\. The malignancies are refractory to standard systemic therapy or there is no available systemic therapy.
* 4\. Followings are the diseases entities which are limited in each part:

  * a. Dose escalation phase (cohort 1): non-small cell lung cancer, small cell lung cancer, gastric cancer, neuroendocrine carcinoma, biliary tract cancer (including intrahepatic cholangiocarcinoma \[CCA\], extrahepatic CCA, gallbladder cancer, ampullary cancer), ovarian cancer, esophageal cancer, thymoma or thymic carcinoma.
  * b. Dose expansion phase (cohort 2): only thymic carcinoma.
* 5\. Radiologically measurable disease as defined by RECIST v1.1.
* 6\. Baseline ECOG performance status score 0-1.
* 7\. Life expectancy of at least 12 weeks.
* 8\. Adequate hematologic parameters, and hepatic and renal functions defined as

  * a. Absolute neutrophil count ≥ 1500 /μL (without growth factor support at least 7 days).
  * b. Platelets ≥ 90000 /μL (evaluated at least 7 days after last platelet transfusion).
  * c. Hemoglobin ≥ 9 g/dL (evaluated at least 14 days after last RBC transfusion).
  * d. Total bilirubin ≤ 1.5X ULN.
  * e. AST/ALT ≤ 2.5X ULN (≤ 5X ULN if attributable to liver metastases).
  * f. serum creatinine ≤ 1.5 x ULN or creatinine clearance rate (CCr) ≥ 50 mL/min (calculated by Cockcroft-Gault formula \[CCr={((140-age) x weight \[kg\])/(72x serum creatinine \[mg/dL\])}x 0.85 (if female)\] or 24-hour urine collection).
* 9\. Normal ECG or ECG without any clinical significant findings.
* 10\. Able to understand and sign an informed consent (or have a legal representative who is able to do so).
* 11\. Women or men of reproductive potential should agree to use an effective contraceptive method.

Exclusion Criteria:

* 1\. Patients who have major surgery, radiotherapy or other systemic chemotherapy or immunotherapy within 3 weeks are not eligible. Patients who have palliative radiotherapy will be eligible if the irradiated area does not involve the only lesion of measurable / evaluable disease.
* 2\. Patient with history of severe allergy to liposomal irinotecan (nal-IRI; ONIVYDE®) or cisplatin.
* 3\. Significant cardiovascular impairment: (1) history of congestive heart failure greater than New York Heart Association (NYHA) Class II, left ventricular ejection fraction\< 50%; or (2) unstable angina, myocardial infarction or stroke within 6 months; or (3) uncontrolled cardiac arrhythmia.
* 4\. Patients with electrolyte abnormalities that have not been corrected.
* 5\. Patients with active metastatic lesions in central nervous system, or need prednisolone ≥ 10 mg/day to control related symptoms
* 6\. Patients with active bacterial, fungal, tuberculosis or human immunodeficiency virus infection
* 7\. Patients with positive hepatitis B surface antigen (HBsAg) but not receiving anti-hepatitis B drug. Patients who have positive HBsAg, positive anti-HBc, or positive anti-HCV are eligible if the corresponding HBV-DNA or HCV-RNA are undetectable.
* 8\. Subjects who have not recovered adequately from any toxicity from other anti-cancer treatment regimens and/or complications from major surgery prior to starting therapy.
* 9\. Patients who have peripheral neuropathy \> grade I of any etiology.
* 10\. Patients who have serious concomitant systemic disorders incompatible with the study, i.e. poorly controlled diabetes mellitus, auto-immune disorders, or other condition that in the opinion of the investigator would preclude the subject's participation in the study.
* 11\. Patients who have other prior or concurrent malignancy except for adequately treated in situ carcinoma or basal cell carcinoma of skin, or any malignancy which remains disease-free for 3 or more years after curative treatment.
* 12\. Females who are breastfeeding or pregnant at screening or baseline.
* 13\. Patients with psychiatric illness which would preclude study compliance.
* 13\. Patients with psychiatric illness which would preclude study compliance.
* 14\. Patients who have received any prior treatment with ONIVYDE® (liposomal irinotecan) or irinotecan-containing regimens