A Phase II Study of Gimatecan (ST1481) in Locally Advanced or Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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This phase II clinical trial studies the safety and effect of as second-line treatmen in local advanced or metastatic pancreatic cancer. The Gimatecan will be given every four weeks.

Official Title
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Gimatecan (ST1481) as Second-line Treatment for Locally Advanced or Metastatic Pancreatic Cancer: an Open-label, Randomized, Controlled Phase II Study

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Gimatecan
* Drug: tegafur, gimeracil and oteracil potassium
* Drug: gemcitabine


Participation Criteria
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Eligibility Criteria
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Key inclusion Criteria: Histologically or cytologically confirmed pancreatic cancer originating from pancreatic ductal epithelium, excluding pancreatic endocrine tumor; Locally advanced or metastatic pancreatic cancer in no condition for radical radiotherapy or operation; Failed in first-line gemcitabine or fluorouracil drugs chemotherapy (Recurrence within 6 months after treatment, progression or toxicity intolerance during treatment); Chemotherapy, targeted therapy or radical radiotherapy should be stopped 3 weeks ago, immunotherapy should be stopped 4 weeks ago, and previous toxicity recovered (CTCAE ≤ level 1); Measurable cancer lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; No younger than 18 years old of either gender; Eastern Cooperative Oncology Group (ECOG) performance status score 0-1; Estimated life expectancy >3 months; The function of important organs meets the following requirements: absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 85×109/L, hemoglobin ≥ 90g/L; serum creatinine ≤ 1.5×ULN, creatinine clearance rate ≥60 mL/min, U-pro < 2+ or 1.0g/L; if U-pro ≥2+ or 1.0g/L, 24 hours U-pro ≤ 1.0g/L can be included; total bilirubin ≤ 1.5×ULN, obstructive jaundice with biliary drainage: total bilirubin ≤ 2.0×ULN; alanine transaminase and aspartate aminotransferase ≤ 2.5×ULN, liver metastasis ≤ 5.0×ULN; serum albumin ≥ 30g/L; Without a history of allergy or hypersensitivity to camptothecin drugs; Taking drugs orally; Serum human chorionic gonadotropin negative in premenopausal women; female patients of childbearing potential and male patients with female partners of childbearing potential must be willing to avoid pregnancy; Ability to understand the study and sign informed consent. Key exclusion Criteria: Patients who have been previously treated with camptothecin drugs or topoisomerase I inhibitor within 6 months before enrollment; Patients who have been previously treated with gemcitabine and fluorouracil in first-line treatment within 6 months before enrollment; Patients who have been previously treated with other investigational drugs within 4 weeks before enrollment; Patients with brain or meningeal metastasis; Patients with a history of gastrointestinal disease which affects drug absorption; Patients with serous cavity effusion with clinical symptoms (such as pleural effusion, peritoneal effusion, pericardial effusion, etc.), which continue to increase after two-week conservative treatment (excluding puncture drainage); Patients with hypertension that cannot be controlled by drugs (≥ 160/100mmhg); angina pectoris within 3 months before enrollment or unstable angina pectoris; myocardial infarction within 1 year before enrollment and cardiac insufficiency (NYHA ≥ II); Patients with active infections requiring systemic treatment or pyrexia of unknown origin prior to initial administration (except neoplastic fever); Patients with hepatitis B surface antigen positive and peripheral blood hepatitis B virus DNA ≥1.0×103 copy/mL; positive of hepatitis C antibody and peripheral blood hepatitis C virus RNA; Patients with active pulmonary tuberculosis or uncontrolled pulmonary tuberculosis after anti-tuberculosis treatment; Patients with a history of immunodeficiency (including a positive HIV test result), or other acquired or congenital immunodeficiency diseases; Patients with a history of malignancies other than pancreatic cancer before enrollment, excluding non-melanoma skin cancer, in situ cervical cancer, or malignant tumors that have been cured for 5 years; Pregnant or lactating women; Patients with a history of mental diseases (including epilepsy or dementia).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gimatecan group<br>All patients will receive gimatecan (0.8mg/m2, on days 1 to 5, PO, every 4 weeks) until progressive disease (PD). | Drug: Gimatecan<br>* Patients will receive gimatecan orally at 0.8mg/m2 on day 1-5 every 4 weeks.<br>* Other names: ST1481;|
| Placebo Comparator: placebo group<br>All patients will receive tegafur, gimeracil and oteracil potassium (40-60mg, twice daily, on days 1 to 14 , PO, every 3 weeks) or gemcitabine (1000mg/m2, on days 1、8, IV, every 3 weeks) until progressive disease (PD). | Drug: tegafur, gimeracil and oteracil potassium<br>* Patients will receive tegafur, gimeracil and oteracil potassium orally at 40 or 60mg twice daily on days 1 to 14 every 3 weeks.<br>Drug: gemcitabine<br>* Patients will receive gemcitabine IV at 1000mg/m2 on days 1、8 every 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | The 2-year progression free survival of the whole group. | From date of randomization until the date of death from any cause or the date of first documented disease progression whichever came first, assessed up to 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The 2-year overall survival of the whole group. | From date of randomization until the date of death from any cause or the date of last follow-up whichever came first, assessed up to 24 months. | 
| Objective response rate (ORR) | Percentage of patients with objective response assessed by best overall. | To evaluate objective response rate every 6 weeks after the initiation of chemotherapy, up to 24 months. | 
| Duration of Response (DoR) | The duration is measured from the first documented response (CR or PR, whichever is first recorded) until the first assessment of Progressive Disease (PD). | First documented CR or PR, whichever is first recorded until the first assessment of PD, assessed up to 24 months. | 
| Disease control rate (DCR) | Percentage of patients with disease control as assessed by best overall. | To evaluate disease control rate every 6 weeks after the initiation of chemotherapy, up to 24 months. | 
| Patient-reported outcome (PRO) | Change from baseline assessed according to the quality of life questionnaire C30. | To evaluate every 6 weeks after the initiation of chemotherapy, up to 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic Cancer, chemotherapy, gimatecan