A Study of Oral Gimatecan in Platinum-Resistant Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer

Study Overview
=================
Brief Summary
-----------------
This phase II clinical trial studies the safety and effect of Gimatecan in patients with platinum-resistant recurrent epithelial ovarian, fallopian tube or peritoneal cancer. The chemotherapy will be given every four weeks.This study is a single-arm, multi-center research design.

Detailed Description
-----------------
The study had 3 phases: screening phase, treatment phase and follow-up phase. During the treatment phase, the drug will continue to be administered until the progression of disease, complete remission , unacceptable toxicity.

Official Title
-----------------
A Phase II Study of Gimatecan in the Treatment of Platinum-resistant Recurrent Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer

Conditions
-----------------
Epithelial Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer

Intervention / Treatment
-----------------
* Drug: Gimatecan


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subjects were able to understand the informed consent, voluntarily participate in and sign the informed consent, with good compliance and cooperation with follow-up. A histopathological or cytological diagnosis of epithelial ovarian, fallopian tube or peritoneal cancer. Previous systematic treatment ≤ 2 lines, and progression in platinum based regimens or recurrence within 6 months after the end of platinum regimen. 1) Imaging progression of recurrence and progression should be clearly recorded;2) Neoadjuvant + adjuvant chemotherapy with platinum regimen ≥ 6 cycles, and platinum regimen after recurrence / progression ≥ 4 cycles;3) If there is progression during the treatment of platinum based regimen, the treatment cycle is not limited;4) Recurrence / progression within 6 months after the end of neoadjuvant / adjuvant therapy is considered to have received the first-line systematic treatment. Measurable cancer lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; ≥18 years old; Eastern Cooperative Oncology Group(ECOG) performance status score 0-1; Estimated life expectancy >3 months; The function of important organs meets the following requirements: white blood cell count (WBC) ≥ 3.0×109/L, absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets ≥ 100×109/L, hemoglobin ≥ 90g/L; ALT, AST≤ 2.5×ULN; liver metastasis: ALT、AST≤ 5.0×ULN; serum albumin ≥ 28g/L; total bilirubin ≤ 1.5×ULN; serum creatinine ≤ 1.5×ULN, creatinine clearance rate ≥60 mL/min; PT≤ 1.5×ULN; The subjects had no history of allergy to camptothecin or its components; Non surgical sterilization or female subjects of childbearing age need to use a medically approved contraceptive method after signing the informed consent, during the study treatment period and within 6 months after the end of the study treatment period; non surgical sterilization female subjects of childbearing age must have negative blood HCG test within 3 days before entering the study; and they must be in non lactation period. Taking drugs orally; The subjects had recovered and treatment will start more than 4 weeks after the end of previous surgery, chemotherapy, targeted therapy and radiotherapy. Exclusion Criteria: Subjects who have been treated previously with topotecan, Irinotecan or other topoisomerase I inhibitors; Other anticancer therapy including any investigational agent within 30 days prior to the first dose of the investigational drug gimatecan; Within 14 days before the first dose of the investigational drug gimatecan, any active infection requiring systemic anti infective treatment; Subjects with a history of major gastrointestinal surgery (e.g., total gastrectomy, small bowel resection) or gastrointestinal dysfunction that may alter drug absorption and activity in vivo; Severe cardiovascular disease, such as NYHA grade 3-4 heart failure; Patients who have been treated previously with intravenous or oral drugs that affect CYP isoenzymes within 7 days prior to the first dose of the investigational drug gimatecan; A history of immunodeficiency (including a positive HIV test result);Presence of active hepatitis B , hepatitis C (positive for hepatitis C antibody, and HCV-RNA levels higher than the lower limit of the assay); Pleural effusion, pericardial effusion or ascites with clinical symptoms can not be controlled by puncture drainage or other treatment; Subjects with hereditary or acquired bleeding tendency (hemophilia, thrombocytopenia, etc.), interstitial pneumonia or pulmonary fibrosis, and active tuberculosis (whether or not treated) in the past year; Vaccinated with live attenuated vaccine within 4 weeks; Subjects had other active malignancies within 5 years before the first dose of the investigational drug gimatecan; Subjects with active meningeal metastasis or uncontrollable and untreated brain metastasis. Other considered unsuitable for the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gimatecan group<br>In Phase II study, patients will receive gimatecan at fixed dose level (0.8mg/m2/d, oral, every 4 weeks) until progressive disease (PD)、complete remission（CR）). | Drug: Gimatecan<br>* Patients will receive gimatecan orally at the fixed dose level on day 1-5 every 4 weeks.<br>* Other names: ST1481;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Percentage of patients with objective response assessed by best overall response (BOR) and independent review committee （IRC） of either complete response(CR) or partial remission(PR) will be reported. | To evaluate objective response rate every 8 weeks after the initiation of chemotherapy, up to 24 months. | 

Secondary 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. | 
| Disease control rate (DCR) | will be reported. | To evaluate disease control rate every 8 weeks after the initiation of chemotherapy, up to 24 months. | 
| Duration of Response (DoR) | 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. | 
| 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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Platinum resistant, epithelial ovarian, fallopian tube or peritoneal cancer, chemotherapy, gimatecan