K-001 Treatment of Advanced Pancreatic Cancer: Clinical Trial of Monotherapy's Tolerability

According to past experience to toxicology studies and clinical test, K-001 at a dose of 2700mg/day has a good safety profile for human body. Upon observation, pancreatic cancer patients receiving a medication at 2160mg/day (1080mg BID) have had good therapeutic efficacy, no sign of significant toxicity.

Dosing regimen:

Phase I clinical test: maximum dose of monotherapy at 2700mg/day. Four groups of repeated administration of monotherapy, at least 3 patients for each group.

Group A: 2700mg/d (1350mg BID); Group B: 3240mg/d (1620mg BID); Group C: 3780mg/d (1890mg BID); Group D: 4320mg/d (2160mg BID). Twice a day, to be taken with warm water on an empty stomach; 4 weeks' administration for each group.

In case of severe adverse reactions associated with the test drug, or if half of the participants show adverse reactions at Ⅲ level and above, the test should be terminated. The maximum dosage not causing the above-described situation shall be considered as the maximum tolerated dose or the biologically effective dose. After the test, continuous medication shall be given upon request from patients.

Inclusion criteria

Disease-related criteria for inclusion:

• Based on histodiagnosis or cytodiagnosis;
• Locally advanced or metastatic pancreatic adenocarcinoma;
• Failure of standard treatment, >28 days after the last chemotherapy;
• Patients not suitable for or having given up standard treatment;
• At least one lesion measurable according to RECIST V 1.0 criteria;
• ECOG score: 0～1;
• Expected survival: ≥3 months;

Haematological, biochemical and organ functions:

• Hematological indices:

• Absolute neutrophil count: ≥1.5×109/L;
• Platelet count: ≥80×109/L;
• Hemoglobin: ≥9.0 g/dL.
• Total bilirubin: ≤1.5 x ULN, albumin: ≥3.0g/dL;
• Patients without liver metastasis: ALT (SGPT) & AST (SGOT) ≤3.0 x ULN Patients with liver metastasis: ALT (SGPT) & AST (SGOT)≤5.0 x ULN;
• Renal functions: serum creatinine ≤ 1.5xULN, Ccr ≥ 60ml/min (Cockcroft-Gault);

General criteria for inclusion:

• Age: 18～70;
• Letter of Consent signed by the patient or his/her legal representative:
• Women of childbearing age must have a urine pregnancy test within 7 days before starting treatment, only negative results shall be included in the group. Male and female patients of childbearing age have agreed to use a reliable method of contraception before and during participating the study as well as 90 days (at least) after withdrawal.

Exclusion criteria

Disease-related criteria for exclusion:

• Patients of pancreatic tumor but not adenocarcinoma;
• Having received radiotherapy for his/her target lesions prior to this study, with no progress;
• Known presence of brain metastases or leptomeningeal metastases;
• With Vater's ampulla cancer or bile duct cancer;
• Partial or complete intestinal obstruction;
• History of other malignancies in past five years, except for:

• A consecutive 5-year disease-free survival from single surgery of other malignancies;
• Cured basal cell carcinoma and cured cervical carcinoma in situ.

General criteria for exclusion:

• Pregnant or breast-feeding women;
• Any unstable systemic disease, including: active infection; hypertension uncontrollable by medication (≥160/100mmHg); unstable angina, or angina with the onset from within the last three months; congestive heart failure (≥level II according to New York Heart Association [NYHA], see Annex 4); myocardial infarction occurred within 1 year before the enrollment; severe arrhythmias requiring medical treatment; and mental disorders, etc.;
• Presence of active hepatitis B (history of hepatitis B infection, whether with or without medication, HBV DNA≥104 copy number or ≥2000u/ml) or HCV-Ab positive; known HIV-positive patients (no clinical signs or symptoms suggesting exemption of HIV test for HIV-infected individuals);
• Having received any of the following treatment within specific time period before inclusion:

• Having had a major surgery within 4 weeks before inclusion;
• Having received expanded scope of radiotherapy within 4 weeks, or having received limited scope of radiotherapy within 2 weeks before inclusion;
• Having participated in any other therapeutic/interventive clinical trials within 4 weeks before inclusion, or taking part in an ongoing trial.
• With CTCAE toxicity at level II or above (excluding hair loss or skin pigmentation), uncured and caused by any previous treatment;
• Not fitting in the study, as conceived by the researcher.