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

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ClinicalTrials.gov Identifier: NCT03693248
Recruitment Status : Recruiting
First Posted : October 2, 2018
Last Update Posted : December 10, 2019
Sponsor:
Information provided by (Responsible Party):
Hee Seung Kim, Seoul National University Hospital

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.


Condition or disease Intervention/treatment Phase
Ovarian Cancer Stage IIIC Ovarian Cancer Stage IV Fallopian Tube Cancer Peritoneal Cancer Drug: Two cycles of neoadjuvant chemotherapy Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 298 participants
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: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 19, 2018
Estimated Primary Completion Date : December 31, 2023
Estimated Study Completion Date : December 31, 2023


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 Name: 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.



Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. Tumor response 1 [ Time Frame: 3 weeks after completion of neoadjuvant chemotherapy, up to 6 weeks ]
    Tumor response after neoadjuvant chemotherapy

  4. Tumor response 2 [ Time Frame: 3 weeks after completion of interval debulking surgery, up to 6 weeks ]
    Surgical response after interval debulking surgery

  5. Tumor response 3 [ Time Frame: 3 weeks after completion of adjuvant chemotherapy, up to 6 weeks ]
    Tumor response after adjuvant chemotherapy

  6. 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

  7. Functional assessment of residual tumor [ Time Frame: 3 weeks after neoadjuvant chemotherapy, up to 6 weeks ]
    Standardized uptake positron emission tomography (PET) CT

  8. 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)

  9. 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)

  10. 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)

  11. 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)

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. Estimated blood loss [ Time Frame: after interval debulking surgery up to 3 months ]
    Estimated blood loss (ml) based on Modified KGOG Operation Record Form

  18. Operation time [ Time Frame: after interval debulking surgery up to 3 months ]
    Operation time (min) based on Modified KGOG Operation Record Form

  19. 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

  20. days of hospitalization [ Time Frame: after interval debulking surgery up to 3 months ]
    days of hospitalization based on Modified KGOG Operation Record Form

  21. 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



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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03693248


Contacts
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Contact: Hee Seung Kim, MD/PhD 82-2-2072-4863 bboddi0311@gmail.com
Contact: Soo Jin Park, MD 82-2-2072-4863 soojin.mdpark@gmail.com

Locations
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Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Moon Kyoung Bae    82-2-2072-2643    mose79bmk@naver.com   
Contact: Soo Jin Park, MD    MD    soojin.mdpark@gmail.com   
Principal Investigator: Hee Seung Kim, MD/PhD         
Sponsors and Collaborators
Seoul National University Hospital
Investigators
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Principal Investigator: Hee Seung Kim, MD/PhD Seoul National University Hospital
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hee Seung Kim, Associate Professor, Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT03693248    
Other Study ID Numbers: 2018-0228
First Posted: October 2, 2018    Key Record Dates
Last Update Posted: December 10, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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
Keywords provided by Hee Seung Kim, Seoul National University Hospital:
advanced ovarian cancer
advanced fallopian cancer
advanced peritoneal cancer
neoadjuvant chemotherapy
cycles of chemotherapy
survival
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Fallopian Tube Neoplasms
Peritoneal Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Fallopian Tube Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action