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

Sponsor:

Collaborators:

Information provided by (Responsible Party):

Hee Seung Kim，Seoul National University Hospital

Tracking Information

First Submitted Date ^ICMJE

July 13, 2018

First Posted Date ^ICMJE

October 2, 2018

Last Update Posted Date

October 4, 2018

Actual Study Start Date ^ICMJE

November 1, 2018

Estimated Primary Completion Date

December 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^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

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^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

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^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

Brief Summary

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.

Detailed Description

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.

Study Type ^ICMJE

Interventional

Study Phase

Phase 3

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Comparison of clinical outcomes between two and three cycles of neoadjuvant chemotherapy followed by interval debulking surgery.
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

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

Study Arms

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.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

298

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

December 31, 2023

Estimated Primary Completion Date

December 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria ^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

Sex/Gender

Sexes Eligible for Study:

Female

Ages

20 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Korea, Republic of

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

Plan to Share IPD:

Undecided

Responsible Party

Hee Seung Kim，Seoul National University Hospital

Study Sponsor ^ICMJE

Seoul National University Hospital

Collaborators ^ICMJE

Investigators ^ICMJE

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

PRS Account

Seoul National University Hospital

Verification Date

October 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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