Platinum-based neoadjuvant chemotherapy (NACT) followed by interval debulking surgery is a crucial treatment paradigm for advanced ovarian cancer. It can reduce tumor burden, increase the rate of R0 resection, and decrease surgical complications. The combination of paclitaxel and carboplatin is the standard NACT regimen for ovarian cancer; however, it has limitations: 1) The myelotoxicity of platinum agents may disrupt treatment continuity, and 2) Platinum-based NACT often induces the earlier development of platinum resistance. Therefore, there is a need to explore novel regimens that, while maintaining therapeutic efficacy, can reduce drug exposure and toxicity, delay platinum exposure, and postpone the onset of platinum resistance. Previous research has revealed that PARK2 can degrade phosphorylated BCL2, thereby enhancing sensitivity to paclitaxel. We established a PARK2-based molecular classification and found that 57% of advanced ovarian cancer cases exhibit high PARK2 expression. Furthermore, ovarian cancers with high PARK2 expression are highly sensitive to paclitaxel. In these patients, a platinum-free paclitaxel regimen demonstrated superior progression-free survival compared to paclitaxel-platinum combination therapy. Based on these findings, we hypothesize that for PARK2-high advanced ovarian cancer, neoadjuvant chemotherapy with single-agent paclitaxel could reduce toxicity and delay premature platinum exposure while achieving efficacy comparable to the standard doublet regimen. To test this scientific hypothesis, our team plans to conduct an exploratory clinical study. We will enroll patients with advanced, treatment-naive, surgically unresectable, PARK2-high ovarian cancer and randomize them into two cohorts: one receiving neoadjuvant single-agent paclitaxel and the other receiving neoadjuvant paclitaxel plus carboplatin. The study aims to evaluate the efficacy and safety of single-agent paclitaxel NACT in this specific patient population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Paclitaxel 175mg/m2 administered intravenously, repeated every 21 days, for 3 to 4 cycles
Paclitaxel 175mg/m2 intravenous infusion; followed by carboplatin AUC 5\~6 intravenous infusion; repeated every 21 days, for 3\~4 courses.
The proportion of patients with a chemotherapy reaction score of 3 (CRS3)
Time frame: Perioperative/Periprocedural
Incidence of grade 3-4 neutropenia
Time frame: During the 2-year follow-up period, from the start of randomization to the patient's withdrawal from the study
Satisfactory tumor reduction rate
Time frame: Perioperative/Periprocedural
R0 resection rate
Time frame: Perioperative/Periprocedural
Surgical complexity
The measurement that will be used to assess this outcome measure is the Aletti Surgical Complexity Score (SCS), also known as the Surgical Complexity Scoring System for advanced ovarian cancer. This validated scoring system quantifies the complexity of cytoreductive surgery by assigning a weighted point value to specific surgical procedures performed within three anatomical compartments (upper abdomen, mid abdomen, and pelvis). Procedures such as bowel resection, diaphragmatic surgery, splenectomy, and extensive peritonectomy contribute to a total score, which categorizes the surgical effort as low, intermediate, or high complexity.
Time frame: Perioperative/Periprocedural
Progression-free survival (PFS)
Time frame: During the 2-year follow-up period, the time elapsed from the start of randomization to disease progression or death
Objective response rate (ORR)
Time frame: During the 2-year follow-up period, from patient randomization to the tumor volume reduction reaching 30%
Incidence of platinum resistance in first recurrence
Time frame: After the treatment, the disease recurred within 6 months
Overall survival (OS)
Time frame: During the 2-year follow-up period, the time elapsed from randomization to death
Quality of Life (QoL)
Quality of Life, measured by the European Organisation for Research and Treatment of Life Questionnaire-Core 30 (EORTC QLQ-C30), version 3.0 (score range: 0-100; higher scores in global health status/functional scales indicate better quality of life, whereas higher scores in symptom scales indicate worse symptoms) and the ovarian cancer-specific module 28-item (QLQ-OV28) questionnaire. Data will be collected via paper-based questionnaires before treatment initiation and during treatment, and via paper-based questionnaires or telephone interviews during the survival follow-up period. The assessment will be terminated upon patient death, withdrawal of informed consent, or upon disease recurrence or metastasis (regardless of whether the randomly assigned treatment is discontinued).
Time frame: During the 2-year follow-up period, from the beginning of randomization to the end of the study
Incidence of treatment-related adverse events (TRAEs)
Time frame: During the 2-year follow-up period, from the time of randomization to the time when the patient was discharged from the study
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