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

Brief Title

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

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

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 Phase

Phase 3

Study Type

Interventional

Primary Outcome

Progression free survival

Secondary Outcome

 Overall survival

Condition

Ovarian Cancer Stage IIIC

Intervention

Two cycles of neoadjuvant chemotherapy

Study Arms / Comparison Groups

 Two cycles of neoadjuvant chemotherapy

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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

298

Start Date

December 19, 2018

Completion Date

December 31, 2023

Primary Completion Date

December 31, 2023

Eligibility 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
      

Gender

Female

Ages

20 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Hee Seung Kim, MD/PhD, 82-2-2072-4863, [email protected]

Location Countries

Korea, Republic of

Location Countries

Korea, Republic of

NCT ID

NCT03693248

Organization ID

2018-0228

Responsible Party

Principal Investigator

Study Sponsor

Seoul National University Hospital

Study Sponsor

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

Verification Date

December 2019