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

Primary Purpose

Ovarian Cancer Stage IIIC, Ovarian Cancer Stage IV, Fallopian Tube Cancer

Status
Recruiting
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Two cycles of neoadjuvant chemotherapy
Sponsored by
Seoul National University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer Stage IIIC focused on measuring advanced ovarian cancer, advanced fallopian cancer, advanced peritoneal cancer, neoadjuvant chemotherapy, cycles of chemotherapy, survival

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Seoul National University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Two cycles of neoadjuvant chemotherapy

Three cycles of neoadjuvant chemotherapy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Progression free survival
the time interval from randomization date to disease recurrence or progression date

Secondary Outcome Measures

Overall survival
the time interval from randomization date to death or end of study date
Time to progression
the time interval from randomization date to disease recurrence or progression except death date
Tumor response 1
Tumor response after neoadjuvant chemotherapy
Tumor response 2
Surgical response after interval debulking surgery
Tumor response 3
Tumor response after adjuvant chemotherapy
Radiologic evaluation of residual tumor
Size of post operative residual tumor on computed tomography (CT) after interval debulking surgery
Functional assessment of residual tumor
Standardized uptake positron emission tomography (PET) CT
Assessment of quality of life1
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
Scoring of quality of life assessment using the EORTC ovarian cancer module (EORTC QLQ-Ov28)
Assessment of quality of life3
Scoring of quality of life assessment using the Functional Assessment of Cancer Therapy (FACT-O)
Assessment of quality of life4
Scoring of quality of life assessment using the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Adverse events
Evaluation of chemotherapy induced toxicity
Success rate of optimal cytoreduction
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)
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
Incidence of early complications, and severity of complications based on Memorial Sloan Kettering Cancer Center Surgical Secondary Events Grading System
Postoperative complications 2
Incidence of late complications, and severity of complications based on Memorial Sloan Kettering Cancer Center Surgical Secondary Events Grading System
Estimated blood loss
Estimated blood loss (ml) based on Modified KGOG Operation Record Form
Operation time
Operation time (min) based on Modified KGOG Operation Record Form
Transfusion
Transfusion (count by volume of transfused RBC) based on Modified KGOG Operation Record Form
days of hospitalization
days of hospitalization based on Modified KGOG Operation Record Form
days of management in intensive care unit
days of management in intensive care unit based on Modified KGOG Operation Record Form

Full Information

First Posted
July 13, 2018
Last Updated
December 7, 2019
Sponsor
Seoul National University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03693248
Brief Title
Reduction Of Cycles of neOadjuvant Chemotherapy for Advanced Epithelial Ovarian, Fallopian and Primary Peritoneal Cancer
Acronym
ROCOCO
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2019
Overall Recruitment Status
Recruiting
Study Start Date
December 19, 2018 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seoul National University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer Stage IIIC, Ovarian Cancer Stage IV, Fallopian Tube Cancer, Peritoneal Cancer
Keywords
advanced ovarian cancer, advanced fallopian cancer, advanced peritoneal cancer, neoadjuvant chemotherapy, cycles of chemotherapy, survival

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Comparison of clinical outcomes between two and three cycles of neoadjuvant chemotherapy followed by interval debulking surgery.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
298 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Two cycles of neoadjuvant chemotherapy
Arm Type
Experimental
Arm Description
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.
Arm Title
Three cycles of neoadjuvant chemotherapy
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Two cycles of neoadjuvant chemotherapy
Other Intervention Name(s)
paclitaxel and carboplatin
Intervention Description
Two and three cycles of neoadjuvant chemotherapy will be administered in experimental and control groups, respectively
Primary Outcome Measure Information:
Title
Progression free survival
Description
the time interval from randomization date to disease recurrence or progression date
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
Secondary Outcome Measure Information:
Title
Overall survival
Description
the time interval from randomization date to death or end of study date
Time Frame
From the date of randomization until death due to any cause, assessed up to 60 months
Title
Time to progression
Description
the time interval from randomization date to disease recurrence or progression except death date
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
Title
Tumor response 1
Description
Tumor response after neoadjuvant chemotherapy
Time Frame
3 weeks after completion of neoadjuvant chemotherapy, up to 6 weeks
Title
Tumor response 2
Description
Surgical response after interval debulking surgery
Time Frame
3 weeks after completion of interval debulking surgery, up to 6 weeks
Title
Tumor response 3
Description
Tumor response after adjuvant chemotherapy
Time Frame
3 weeks after completion of adjuvant chemotherapy, up to 6 weeks
Title
Radiologic evaluation of residual tumor
Description
Size of post operative residual tumor on computed tomography (CT) after interval debulking surgery
Time Frame
3 weeks after interval debulking surgery, up to 6 weeks
Title
Functional assessment of residual tumor
Description
Standardized uptake positron emission tomography (PET) CT
Time Frame
3 weeks after neoadjuvant chemotherapy, up to 6 weeks
Title
Assessment of quality of life1
Description
Scoring of quality of life assessment using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
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
Title
Assessment of quality of life2
Description
Scoring of quality of life assessment using the EORTC ovarian cancer module (EORTC QLQ-Ov28)
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
Title
Assessment of quality of life3
Description
Scoring of quality of life assessment using the Functional Assessment of Cancer Therapy (FACT-O)
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
Title
Assessment of quality of life4
Description
Scoring of quality of life assessment using the EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
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
Title
Adverse events
Description
Evaluation of chemotherapy induced toxicity
Time Frame
From the date of first day of chemotherapy to the day before starting next cycle. Each cycle is 21 days.
Title
Success rate of optimal cytoreduction
Description
Evaluation of optimal cytoreduction and extent of resection based on modified Korean Gynecologic Oncology Group (KGOG) operation record form and tumor burden index
Time Frame
On the date of completion of interval debulking surgery, up to 24 hours
Title
Surgical complexity score (SCS)
Description
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.
Time Frame
On the date of completion of interval debulking surgery, up to 24 hours
Title
Postoperative complications 1
Description
Incidence of early complications, and severity of complications based on Memorial Sloan Kettering Cancer Center Surgical Secondary Events Grading System
Time Frame
Early complications: after interval debulking surgery, up to 30 days
Title
Postoperative complications 2
Description
Incidence of late complications, and severity of complications based on Memorial Sloan Kettering Cancer Center Surgical Secondary Events Grading System
Time Frame
Late complications: 31 days after interval debulking surgery through study completion, an average of 1 year
Title
Estimated blood loss
Description
Estimated blood loss (ml) based on Modified KGOG Operation Record Form
Time Frame
after interval debulking surgery up to 3 months
Title
Operation time
Description
Operation time (min) based on Modified KGOG Operation Record Form
Time Frame
after interval debulking surgery up to 3 months
Title
Transfusion
Description
Transfusion (count by volume of transfused RBC) based on Modified KGOG Operation Record Form
Time Frame
after interval debulking surgery up to 3 months
Title
days of hospitalization
Description
days of hospitalization based on Modified KGOG Operation Record Form
Time Frame
after interval debulking surgery up to 3 months
Title
days of management in intensive care unit
Description
days of management in intensive care unit based on Modified KGOG Operation Record Form
Time Frame
after interval debulking surgery up to 3 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 Pregnancy 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hee Seung Kim, MD/PhD
Phone
82-2-2072-4863
Email
bboddi0311@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Soo Jin Park, MD
Phone
82-2-2072-4863
Email
soojin.mdpark@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hee Seung Kim, MD/PhD
Organizational Affiliation
Seoul National University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Moon Kyoung Bae
Phone
82-2-2072-2643
Email
mose79bmk@naver.com
First Name & Middle Initial & Last Name & Degree
Soo Jin Park, MD
Phone
MD
Email
soojin.mdpark@gmail.com
First Name & Middle Initial & Last Name & Degree
Hee Seung Kim, MD/PhD

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
32375688
Citation
Park SJ, Shim SH, Ji YI, Kwon SH, Lee EJ, Lee M, Chang SJ, Park S, Kim SY, Lee SJ, Kim JW, Roh JW, Lee SH, Song T, Kim HS. Reduction of cycles of neoadjuvant chemotherapy for advanced epithelial ovarian, fallopian or primary peritoneal cancer (ROCOCO): study protocol for a phase III randomized controlled trial. BMC Cancer. 2020 May 6;20(1):385. doi: 10.1186/s12885-020-06886-2.
Results Reference
derived

Learn more about this trial

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

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