Multi-center, Randomized Controlled, Phase III Trials to Evaluate the Safety and Effectiveness After Cycles Reduction of Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian, Fallopian and Primary Peritoneal Cancer
试验速览
- 阶段
- 3 期
- 入组人数
- 298
- 试验地点
- 1
- 主要终点
- Progression free survival
研究概览
简要总结
Te hypothesized that two cycles of neoadjuvant chemotherapy followed by interval debulking surgery would improve survival in advanced epithelial ovarian, fallopian, and primary peritoneal cancer because reduction of one cycle of chemotherapy can lead to the removal of more tumor burden, compared with three cycles of neoadjuvant chemotherapy.
So the investigators aim to compare survival, rate of successful optimal cytoreductive surgery, post-operative complications, and quality of life between two and three cycles of neoadjuvant chemotherapy followed by interval debulking surgery for advanced epithelial ovarian, fallopian, and primary peritoneal cancer.
详细描述
Primary debulking surgery (PDS) followed by adjuvant chemotherapy is the standard treatment for advanced epithelial ovarian, fallopian and primary peritoneal cancer. However, three or four cycles of neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) has been introduced in clinical setting because four randomized controlled trials related have shown a lower rate of complications in NAC followed by IDS despite the similar efficacy between PDS and NAC followed by IDS in advanced epithelial ovarian, fallopian and primary peritoneal cancers. However, these trials have some limitations that the rate of optimal cytoreduction defined as the size of residual tumor <1 cm was about 40%, which was a disappointed result not showing the surgical effect improving survival. Nevertheless, more treatment strategies using NAC followed by IDS should be investigated because NAC followed by IDS has been already known as another standard treatment due to the safety.
A recent meta-analysis has reported that reduction of one cycle of neoadjuvant chemotherapy may increase overall survival of 4.1 months because it can induce surgical resection of more visible tumors with drug-resistant. Moreover, a related clinical trial has shown that hyperthermic intraperitoneal chemotherapy (HIPEC) may increase survival in patients with advanced ovarian cancer who received three cycles of neoadjuvant chemotherapy because HIPEC can kill drug-resistant invisible tumor cells which were not resected during IDS. Thus, the investigators designed a phase 3, multicenter, randomized controlled trial for comparing survival, clinical outcomes and quality of life between two and three cycles of NAC followed by IDS, and thereby will investigate the efficacy and safety of reduction of one cycle of NAC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age: 20-80 years old
- •Advanced epithelial ovarian, fallopian or primary peritoneal cancer diagnosed with the following methods
- •Histologic confirmation by diagnostic laparoscopic or laparotomy ② Histologic malignancy originated from female genital tract on fine needle aspiration if histological confirmation is difficult or cytologic confirmation of adenocarcinoma in ascites if fine needle aspiration is difficult, meeting the following criteria
- •Existence of the pelvic or ovarian mass
- •Identification of tumor >2 cm beyond the pelvis on CT, malignant pleural effusion by thoracentesis, extraperitoneal lymph node metastasis (cardio-phrenic, internal mammary, mediastinal, para-tracheal, supraclavicular lymph nodes or inguinal lymph nodes)
- •Cancer antigen 125 (CA-125, kU/L)/carcinoembryonic antigen (CEA, ng/ml) >25
- •if CA-125 (kU/L)/CEA (ng/ml) is 25 or less, no primary lesion on colonoscopy, gastroscopy and mammography within six weeks before randomization.
- •International Federation of Gynecology and Obstetrics (FIGO) stage IIIC to IVB disease
- •World Health Organization performance status 0-2
- •The following criteria should be met if synchronous or metachronous tumors exists.
- •① Complete remission of metachronous malignancy for at least 5 years
- •② Follicular or papillary thyroid cancer treated completely with only surgery as a synchronous tumor
- •③ Early gastric or colon cancer treated completely with only endoscopic mucosal resection as a synchronous tumor
- •Normal hematologic, renal and liver function with the following criteria White blood cell (WBC) ≥3,000/ul Absolute neutrophil count (ANC) ≥1,500/ul Platelet ≥100×103/ul Aspartate aminotransferase (AST) ≤100 IU/L Alanine aminotransferase (ALT) ≤100 IU/L Serum total bilirubin ≤1.5 mg/dL Serum creatinine ≤1.5 mg/dL
- •Absence of psychological, and socioeconomic limitations affecting participation to this trial
- •Informed consent
排除标准
- •Diagnosis of metachronous malignancy within five years before enrollment
- •Synchronous tumors except follicular or papillary thyroid cancer treated completely with only surgery and early gastric or colon cancer treated completely with only endoscopic mucosal resection
- •Carcinoma in situ, non-epithelial, or borderline tumor in ovary, fallopian tube, and peritoneum
- •Medical conditions (hypertension, diabetes mellitus, infectious or cardiac disease etc.) influencing on survival
- •Clinical evidence of brain or leptomeningeal metastasis, bone metastasis
- •Other treatments affecting clinical outcomes during participation to this trial (hyperthermic intraperitoneal chemotherapy, onco-thermia, herbal medicine, etc.)
- •No informed consent
研究组 & 干预措施
Two cycles of neoadjuvant chemotherapy
- Paclitaxel (175mg/m2) and carboplatin (AUC 5.0 or 6.0) IV, D1, every three weeks.
- Two cycles of neoadjuvant chemotherapy and four cycles of adjuvant chemotherapy.
干预措施: Two cycles of neoadjuvant chemotherapy (Drug)
结局指标
主要结局
Progression free survival
时间窗: From date of randomization until the date of first documented progression or date of death (by any cause, in the absence of disease progression) whichever came first, assessed up to 60 months
the time interval from randomization date to disease recurrence or progression date
次要结局
- Radiologic evaluation of residual tumor(3 weeks after interval debulking surgery, up to 6 weeks)
- Functional assessment of residual tumor(3 weeks after neoadjuvant chemotherapy, up to 6 weeks)
- Assessment of quality of life2(From the date of screening to the date before treatment start, 3 weeks after interval debulking surgery within 6 weeks, 3 weeks after completion of adjuvant chemotherapy up to 6 weeks, on date of visit at 6 months after completion of primary treatment)
- Postoperative complications 2(Late complications: 31 days after interval debulking surgery through study completion, an average of 1 year)
- Estimated blood loss(after interval debulking surgery up to 3 months)
- Tumor response 2(3 weeks after completion of interval debulking surgery, up to 6 weeks)
- Overall survival(From the date of randomization until death due to any cause, assessed up to 60 months)
- Assessment of quality of life4(From the date of screening to the date before treatment start, 3 weeks after interval debulking surgery within 6 weeks, 3 weeks after completion of adjuvant chemotherapy up to 6 weeks, on date of visit at 6 months after completion of primary treatment)
- Postoperative complications 1(Early complications: after interval debulking surgery, up to 30 days)
- Time to progression(From date of randomization until the date of first documented progression in the absence of death by any cause, assessed up to 60 months)
- Assessment of quality of life3(From the date of screening to the date before treatment start, 3 weeks after interval debulking surgery within 6 weeks, 3 weeks after completion of adjuvant chemotherapy up to 6 weeks, on date of visit at 6 months after completion of primary treatment)
- Adverse events(From the date of first day of chemotherapy to the day before starting next cycle. Each cycle is 21 days.)
- Tumor response 1(3 weeks after completion of neoadjuvant chemotherapy, up to 6 weeks)
- Tumor response 3(3 weeks after completion of adjuvant chemotherapy, up to 6 weeks)
- Operation time(after interval debulking surgery up to 3 months)
- Transfusion(after interval debulking surgery up to 3 months)
- Assessment of quality of life1(From the date of screening to the date before treatment start, 3 weeks after interval debulking surgery within 6 weeks, 3 weeks after completion of adjuvant chemotherapy up to 6 weeks, on date of visit at 6 months after completion of primary treatment)
- Success rate of optimal cytoreduction(On the date of completion of interval debulking surgery, up to 24 hours)
- Surgical complexity score (SCS)(On the date of completion of interval debulking surgery, up to 24 hours)
- days of hospitalization(after interval debulking surgery up to 3 months)
- days of management in intensive care unit(after interval debulking surgery up to 3 months)
研究者
Hee Seung Kim
Associate Professor
Seoul National University Hospital