Clinical trial NCT06437353: Surufatinib Combined With Carboplatin/Paclitaxel and Surufatinib Combined With Olaparib as First-line and Maintenance Therapy for Newly Diagnosed High-risk Ovarian Cancer
Official title: Sorafenib Combined With Carboplatin/Paclitaxel and Sorafenib Combined With Olaparib as First-line and Maintenance Therapy for Newly Diagnosed High-risk Ovarian Cancer: a Single-arm, Multicenter, Exploratory Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: Antiangiogenic
Lead sponsor: Anhui Provincial Cancer Hospital
Sponsor class: OTHER
Collaborators: name: Hutchison Medipharma Limited
First posted: 2024-05-31
Enrollment: 74
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this type of clinical trial study is to evaluate the safety and efficacy of Surufatinib combined with Carboplatin/Paclitaxel and Surufatinib combined with Olaparib as first-line and maintenance therapy for newly diagnosed high-risk ovarian cancer

Detailed description: Patients will have tests and exams to see if they are eligible for the clinical trial.

First-line chemotherapy regimen:

Paclitaxel/Carboplatin(repeat every 3 weeks, total of 6 cycles):

* Paclitaxel: 175 mg/m², intravenous infusion, on day 1.
* Carboplatin: AUC 5, intravenous infusion, on day 1.
* For patients aged ≥70 years or those with comorbidities, the paclitaxel dose can be adjusted to 135 mg/m².

Surufatinib(repeat every 3 weeks, total of 5 cycles):

* Surufatinib is not used during the first postoperative cycle.
* Starting from the second postoperative cycle, surufatinib is administered at a dose of 250 mg once daily, taken continuously.

Maintenance Therapy Regimen:

HRD-positive Patients:

* Surufatinib: 250 mg once daily, taken continuously.
* Olaparib: 300 mg twice daily, with doses taken 12 hours apart. Olaparib can be used for a maximum of 2 years.

HRD-negative or HRD Status Unknown Patients:

* Surufatinib: 250 mg once daily, taken continuously.

Treatment continues until the patient experiences disease progression or meets other criteria for discontinuation of the study treatment as specified in the protocol.

Eligibility criteria: Inclusion Criteria:

1. Age: 18-75 years old (≥18, ≤75)
2. Patients with newly diagnosed FIGO stage III or IV high-grade serous ovarian cancer, high-grade endometrioid carcinoma, primary peritoneal cancer, and/or fallopian tube cancer with high-risk factors for recurrence. High-risk recurrence is defined as follows:

   * FIGO stage III with non-R0 resection;
   * FIGO stage IV;
   * Presence of ascites at initial diagnosis.
3. Patients who have undergone primary debulking surgery (PDS) for ovarian cancer.
4. ECOG performance status score: 0-2.
5. Postoperative administration time ≤12 weeks.
6. Expected survival of at least 3 months.
7. Major organ function within 7 days prior to treatment meets the following criteria:

   * Hemoglobin (HB) ≥90 g/L;
   * Absolute neutrophil count (ANC) ≥1.5×10⁹/L;
   * Platelets (PLT) ≥100×10⁹/L.
8. Biochemical parameters must meet the following standards:

   * Total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN);
   * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN, or ≤5×ULN if liver metastases are present;
   * Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CCr) ≥60 ml/min.
9. Women of childbearing potential must use effective contraception.
10. Subjects must voluntarily join the study and sign the informed consent form (ICF).
11. Subjects are expected to have good compliance and the ability to follow up on efficacy and adverse reactions as required by the protocol.

Exclusion Criteria:

1. Previous treatment with anti-angiogenic drugs such as apatinib, sorafenib, anlotinib, bevacizumab, or other anti-angiogenic therapies.
2. Pregnant or breastfeeding women.
3. Patients who have previously participated in other clinical trials that have not yet concluded.
4. Patients with evidence or history of significant bleeding tendencies or events within 3 months before enrollment (bleeding \>30 mL, accompanied by hematemesis, melena, or hematochezia), hemoptysis (≥5 mL of fresh blood within 4 weeks), or thromboembolic events (including stroke and/or transient ischemic attack) within 12 months.
5. Patients with uncontrolled hypertension (systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg).
6. Patients with grade I or higher myocardial ischemia or infarction, arrhythmias (including QTc ≥480 ms), or ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification).
7. Patients with active or uncontrolled severe infections (≥CTC AE grade 2).
8. Patients with renal failure requiring hemodialysis or peritoneal dialysis.
9. Patients with a history of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency diseases, or those with a history of organ transplantation.
10. Patients with persistent proteinuria (≥++) on two consecutive urine tests, and confirmed 24-hour urine protein \>1.0 g.
11. Patients with psychiatric disorders, including epilepsy, dementia, severe depression, mania, etc.
12. Patients with any signs or history of bleeding disorders, regardless of severity; patients who experienced any bleeding or hemorrhagic event ≥CTCAE grade 3 within 4 weeks before enrollment; patients with unhealed wounds, ulcers, or fractures.
13. Patients who had arterial or venous thrombotic events, such as cerebrovascular accidents (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism, within the past 6 months.
14. Patients with symptomatic brain metastases or those whose symptoms have been controlled for less than 2 months.
15. Patients with a history of substance abuse that cannot be relinquished or those with psychiatric disorders.
16. Patients with difficulty swallowing or known absorption disorders affecting drug intake.
17. Patients allergic to treatment drugs sorafenib or paclitaxel/carboplatin.
18. Any other condition that the researcher deems unsuitable for enrollment.

Primary outcomes:
measure: Progression free survival
timeFrame: 12-month
Secondary outcomes:
measure: Overall Response Rate (ORR
timeFrame: 3-month
measure: Disease control rate
timeFrame: 3-month
measure: Overall survival
timeFrame: 3-years
measure: Adverse event
timeFrame: 3-month
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Cancer Hospital
state: Anhui
Study officials:
affiliation: Anhui Provincial Cancer Hospital
name: Bairong Xia, Doctor
role: STUDY_CHAIR
affiliation: Anhui Provincial Cancer Hospital
name: Wenjing Jiang
role: STUDY_DIRECTOR
References: