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

December 7, 2019 updated by: Hee Seung Kim, Seoul National University Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

298

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Two cycles of neoadjuvant chemotherapy
Two and three cycles of neoadjuvant chemotherapy will be administered in experimental and control groups, respectively
Other Names:
  • paclitaxel and carboplatin
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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 Measures

Outcome Measure
Measure Description
Time Frame
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
From the date of randomization until death due to any cause, assessed up to 60 months
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
From date of randomization until the date of first documented progression in the absence of death by any cause, assessed up to 60 months
Tumor response 1
Time Frame: 3 weeks after completion of neoadjuvant chemotherapy, up to 6 weeks
Tumor response after neoadjuvant chemotherapy
3 weeks after completion of neoadjuvant chemotherapy, up to 6 weeks
Tumor response 2
Time Frame: 3 weeks after completion of interval debulking surgery, up to 6 weeks
Surgical response after interval debulking surgery
3 weeks after completion of interval debulking surgery, up to 6 weeks
Tumor response 3
Time Frame: 3 weeks after completion of adjuvant chemotherapy, up to 6 weeks
Tumor response after adjuvant chemotherapy
3 weeks after completion of adjuvant chemotherapy, up to 6 weeks
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
3 weeks after interval debulking surgery, up to 6 weeks
Functional assessment of residual tumor
Time Frame: 3 weeks after neoadjuvant chemotherapy, up to 6 weeks
Standardized uptake positron emission tomography (PET) CT
3 weeks after neoadjuvant chemotherapy, up to 6 weeks
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)
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
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)
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
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)
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
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)
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
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
From the date of first day of chemotherapy to the day before starting next cycle. Each cycle is 21 days.
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
On the date of completion of interval debulking surgery, up to 24 hours
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.
On the date of completion of interval debulking surgery, up to 24 hours
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
Early complications: after interval debulking surgery, up to 30 days
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
Late complications: 31 days after interval debulking surgery through study completion, an average of 1 year
Estimated blood loss
Time Frame: after interval debulking surgery up to 3 months
Estimated blood loss (ml) based on Modified KGOG Operation Record Form
after interval debulking surgery up to 3 months
Operation time
Time Frame: after interval debulking surgery up to 3 months
Operation time (min) based on Modified KGOG Operation Record Form
after interval debulking surgery up to 3 months
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
after interval debulking surgery up to 3 months
days of hospitalization
Time Frame: after interval debulking surgery up to 3 months
days of hospitalization based on Modified KGOG Operation Record Form
after interval debulking surgery up to 3 months
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
after interval debulking surgery up to 3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 19, 2018

Primary Completion (ANTICIPATED)

December 31, 2023

Study Completion (ANTICIPATED)

December 31, 2023

Study Registration Dates

First Submitted

July 13, 2018

First Submitted That Met QC Criteria

September 29, 2018

First Posted (ACTUAL)

October 2, 2018

Study Record Updates

Last Update Posted (ACTUAL)

December 10, 2019

Last Update Submitted That Met QC Criteria

December 7, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018-0228

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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