Clinical trial NCT05736952: Oral Topotecan Combined With Anlotinib in Patients With Platinum-resistant Recurrent Ovarian Cancer
Official title: Oral Topotecan Combined With Anlotinib in Patients With Platinum-resistant Recurrent Ovarian Cancer：
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Platinum-resistant Ovarian Cancer
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2023-02-21
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate the treatment of topotecan hydrochloride capsules combined with anlotinib hydrochloride capsules in Patients with platinum-resistant recurrent epithelial ovarian cancer. The main questions it aims to answer are: to assess the objective response rate (ORR), progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), overall survival (OS) and safety of topotecan hydrochloride capsules combined with anlotinib hydrochloride capsules in patients with platinum-resistant recurrent epithelial ovarian cancer.The treatment of participants： Topotecan hydrochloride capsules: 2 mg, once daily, oral with dinner for 5 days, discontinued for 16 days, that is, 21 days (3 weeks) as a course of treatment, a total of 6 courses of administration.；Anlotinib hydrochloride capsules: 10mg once a day, oral before breakfast, continuous administration for 14 days, discontinuation for 7 days, that is, 21 days (3 weeks) as a course of treatment. Receiving optimal supportive care at the same time until disease progression/death/intolerable toxicity.


Eligibility criteria: Inclusion Criteria:

1. Age≥ 18 years old;
2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2;
3. The pathological type is epithelial ovarian cancer: high-grade serous, clear cell, endometrium-like; or fallopian tube cancer, primary peritoneal cancer;
4. After surgery, the patient received ≥ 2 lines of chemotherapy,Platinum resistant ovarian cancer (defined as relapsing within 6 months after the last administration of platinum-based chemotherapy);
5. Clinical recurrence with measurable lesions (with imaging evidence);
6. Estimated survival≥ 3 months;
7. The main organs function well, and the examination indicators meet the following requirements: 1) Routine blood test: hemoglobin ≥ 90 g/L (no transfusion within 14 days); Neutrophil count≥ 1.5×109/L; Platelet count≥ 80×109/L; 2) Biochemical examination: Total bilirubin ≤1.5×ULN (upper limit of normal); Blood valley alanine aminotransferase (ALT) or blood valley aminotransferase (AST) ≤ 2.5×ULN; ALT or AST ≤ 5×ULN if liver metastases are present; Serum creatinine ≤ 1.5×ULN or endogenous creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula);
8. Good compliance, family members agree to cooperate with survival follow-up.

Exclusion Criteria:

1. Have other malignant tumors at the same time, except for malignant tumors that have been cured or stabilized;
2. Pregnant or lactating women;
3. Participated in clinical trials of other drugs within six months;
4. Have a variety of factors that affect oral drugs (such as inability to swallow, chronic diarrhea and intestinal obstruction, etc.);
5. Any bleeding event with a severe grade of 3 or above in CTCAE 4.0 within 4 weeks prior to screening;
6. Patients with known central nervous system metastases or history of central nervous system metastases before screening;
7. Patients with hypertension who cannot be well controlled by single antihypertensive drugs (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg); Patients with a history of unstable angina; Patients with a new diagnosis of angina within 3 months before screening or a myocardial infarction event within 6 months before screening; Arrhythmias require long-term use of antiarrhythmic drugs and New York Heart Association grade ≥ II cardiac insufficiency;
8. Long-term unhealed wounds or incompletely healed fractures;
9. Previous organ transplantation history;
10. Imaging shows that the tumor has invaded important blood vessels or the investigator judges that the patient's tumor has a high possibility of invading important blood vessels during treatment and causing fatal hemorrhage;
11. Coagulation dysfunction (prothrombin time\>16s, Activated partial thromboplastin\>43s, thrombin time\>21s, fibrinogen\<2g/L), with bleeding tendency (14 days before randomization must meet: INR within normal value without anticoagulant); Patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or their analogues; Under the premise of the international normalized ratio (INR) of prothrombin time (INR) ≤ 1.5, the use of low-dose warfarin (1 mg orally once daily) or low-dose aspirin (not exceeding 100 mg daily) for prophylactic purposes is permitted;
12. Screen for arteriovenous thrombotic events within one year before, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis (except for venous thrombosis caused by venous catheterization with chemotherapy in the early stage of chemotherapy and judged to have been cured by the investigator) and pulmonary embolism;
13. Those who have a history of psychotropic substance abuse and cannot quit or have mental disorders;
14. Have a history of immunodeficiency, or have other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation;
15. According to the judgment of the investigator, there are serious concomitant diseases that endanger the safety of patients or affect the completion of the study;
16. History of surgical procedures within 28 days;
17. History of abdominal fistula or gastrointestinal perforation within 28 days;
18. Those who may receive other systemic anti-tumor therapy or plan to undergo ovarian cancer debulking surgery during the study.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: one year
Secondary outcomes:
measure: progression-free survival (PFS)
timeFrame: one year
measure: disease control rate (DCR)
timeFrame: one year
measure: duration of response (DOR)
timeFrame: one year
measure: overall survival (OS)
timeFrame: one year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
Study officials:
affiliation: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Xipeng Wang, Dr
role: STUDY_DIRECTOR
References: