Reduction Of Cycles of neOadjuvant Chemotherapy for Advanced Epithelial Ovarian, Fallopian and Primary Peritoneal Cancer

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合作者:

信息的提供 (责任方):

Hee Seung Kim，Seoul National University Hospital

追踪信息

首次提交日期 ^ICMJE

July 13, 2018

首次发布日期e ^ICMJE

October 2, 2018

最后更新发布日期

October 4, 2018

预计研究开始日期 ^ICMJE

November 1, 2018

预计主要完成日期

December 31, 2023 (主要结果测量的最终数据收集日期)

目前主要观察指标 ^ICMJE

Progression free survival[ Time Frame: 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

原始主要观察测量 ^ICMJE

与当前相同

目前的二级观察 ^ICMJE

Overall survival[ Time Frame: From the date of randomization until death due to any cause, assessed up to 60 months ]
the time interval from randomization date to death or end of study date
Time to progression[ Time Frame: From date of randomization until the date of first documented progression in the absence of death by any cause, assessed up to 60 months ]
the time interval from randomization date to disease recurrence or progression except death date
Tumor response 1[ Time Frame: 3 weeks after completion of neoadjuvant chemotherapy, up to 6 weeks ]
Tumor response after neoadjuvant chemotherapy
Tumor response 2[ Time Frame: 3 weeks after completion of interval debulking surgery, up to 6 weeks ]
Surgical response after interval debulking surgery
Tumor response 3[ Time Frame: 3 weeks after completion of adjuvant chemotherapy, up to 6 weeks ]
Tumor response after adjuvant chemotherapy
Radiologic evaluation of residual tumor[ Time Frame: 3 weeks after interval debulking surgery, up to 6 weeks ]
Size of post operative residual tumor on computed tomography (CT) after interval debulking surgery
Functional assessment of residual tumor[ Time Frame: 3 weeks after neoadjuvant chemotherapy, up to 6 weeks ]
Standardized uptake positron emission tomography (PET) CT
Assessment of quality of life1[ Time Frame: 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 ]
Scoring of quality of life assessment using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Assessment of quality of life2[ Time Frame: 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 ]
Scoring of quality of life assessment using the EORTC ovarian cancer module (EORTC QLQ-Ov28)
Assessment of quality of life3[ Time Frame: 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 ]
Scoring of quality of life assessment using the Functional Assessment of Cancer Therapy (FACT-O)
Assessment of quality of life4[ Time Frame: 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 ]
Scoring of quality of life assessment using the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Adverse events[ Time Frame: From the date of first day of chemotherapy to the day before starting next cycle. Each cycle is 21 days. ]
Evaluation of chemotherapy induced toxicity
Success rate of optimal cytoreduction[ Time Frame: On the date of completion of interval debulking surgery, up to 24 hours ]
Evaluation of optimal cytoreduction and extent of resection based on modified Korean Gynecologic Oncology Group (KGOG) operation record form and tumor burden index
Surgical complexity score (SCS)[ Time Frame: On the date of completion of interval debulking surgery, up to 24 hours ]
Evaluation of difficulty of surgical skills based on surgical complexity score Minimal 0 to maxial 18 point. Each surgery will classified into low (point ≤3), intermediate (4-7), high (≥8) Higher value means more complex surgery.
Postoperative complications 1[ Time Frame: Early complications: after interval debulking surgery, up to 30 days ]
Incidence of early complications, and severity of complications based on Memorial Sloan Kettering Cancer Center Surgical Secondary Events Grading System
Postoperative complications 2[ Time Frame: Late complications: 31 days after interval debulking surgery through study completion, an average of 1 year ]
Incidence of late complications, and severity of complications based on Memorial Sloan Kettering Cancer Center Surgical Secondary Events Grading System
Estimated blood loss[ Time Frame: after interval debulking surgery up to 3 months ]
Estimated blood loss (ml) based on Modified KGOG Operation Record Form
Operation time[ Time Frame: after interval debulking surgery up to 3 months ]
Operation time (min) based on Modified KGOG Operation Record Form
Transfusion[ Time Frame: after interval debulking surgery up to 3 months ]
Transfusion (count by volume of transfused RBC) based on Modified KGOG Operation Record Form
days of hospitalization[ Time Frame: after interval debulking surgery up to 3 months ]
days of hospitalization based on Modified KGOG Operation Record Form
days of management in intensive care unit[ Time Frame: after interval debulking surgery up to 3 months ]
days of management in intensive care unit based on Modified KGOG Operation Record Form

描述性信息

简略标题 ^ICMJE

Reduction Of Cycles of neOadjuvant Chemotherapy for Advanced Epithelial Ovarian, Fallopian and Primary Peritoneal Cancer

正式标题 ^ICMJE

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

简要概况

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.

详细说明

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.

研究类型 ^ICMJE

Interventional

研究阶段

Phase 3

研究设计 ^ICMJE

分配: Randomized
干预模型: Parallel Assignment
干预模型描述: Comparison of clinical outcomes between two and three cycles of neoadjuvant chemotherapy followed by interval debulking surgery.
盲法: Interventional
盲法描述:
主要目的: Treatment

适用条件 ^ICMJE

干预项目 ^ICMJE

Drug: Two cycles of neoadjuvant chemotherapy
Two and three cycles of neoadjuvant chemotherapy will be administered in experimental and control groups, respectively

研究工具

Experimental: 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.
No Intervention: Three cycles of neoadjuvant chemotherapy
Paclitaxel (175mg/m2) and carboplatin (AUC 5.0 or 6.0) IV, D1, every three weeks. Three cycles of neoadjuvant chemotherapy and three cycles of adjuvant chemotherapy.

招募信息

招募状态 ^ICMJE

Not yet recruiting

预计入组 ^ICMJE

298

原始预计入组 ^ICMJE

与当前相同

预计研究完成日期

December 31, 2023

预计主要完成日期

December 31, 2023 (主要结果测量的最终数据收集日期)

合格标准 ^ICMJE

Inclusion Criteria: 1. Age: 20-80 years old 2. 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. 3. International Federation of Gynecology and Obstetrics (FIGO) stage IIIC to IVB disease 4. World Health Organization performance status 0-2 5. 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 6. 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 7. Absence of psychological, and socioeconomic limitations affecting participation to this trial 8. Informed consent Exclusion Criteria: 1. Diagnosis of metachronous malignancy within five years before enrollment 2. 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 3. Carcinoma in situ, non-epithelial, or borderline tumor in ovary, fallopian tube, and peritoneum 4. Pregnancy 5. Medical conditions (hypertension, diabetes mellitus, infectious or cardiac disease etc.) influencing on survival 6. Clinical evidence of brain or leptomeningeal metastasis, bone metastasis 7. Other treatments affecting clinical outcomes during participation to this trial (hyperthermic intraperitoneal chemotherapy, onco-thermia, herbal medicine, etc.) 8. No informed consent

性别

参与研究的性别:

Female

年龄

最小年龄：20 Years ，最大年龄：80 Years

接受健康的志愿者

没有

可入组国家 ^ICMJE

Korea, Republic of

管理信息

数据检测委员会

Yes

研究涉及美国FDA监管的产品

研究美国FDA监管的药品: No
研究涉及美国FDA监管的设备产品: No

IPD 共享声明

计划分享 IPD:

Undecided

责任方

Hee Seung Kim，Seoul National University Hospital

研究赞助商 ^ICMJE

Seoul National University Hospital

合作者 ^ICMJE

研究员 ^ICMJE

Principal Investigator: Hee Seung Kim, MD/PhD Seoul National University Hospital

PRS 账户

Seoul National University Hospital

验证日期

October 2018

^ICMJE 国际医学期刊编辑委员会和世界卫生组织 ICTRP 要求的元素

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