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

NCT ID: NCT03693248

Last Updated: 2019-12-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 298 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-19
• Study Completion Date: 2023-12-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Two cycles of neoadjuvant chemotherapy

Intervention Type: DRUG

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

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Two cycles of neoadjuvant chemotherapy

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

Intervention Type: DRUG

Other Intervention Names

paclitaxel and carboplatin

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hee Seung Kim

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hee Seung Kim, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

Seoul National University Hospital

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Hee Seung Kim, MD/PhD

Role: CONTACT

Phone: 82-2-2072-4863

Email: bboddi0311@gmail.com

Soo Jin Park, MD

Role: CONTACT

Phone: 82-2-2072-4863

Email: soojin.mdpark@gmail.com

Facility Contacts

Moon Kyoung Bae

Role: primary

Soo Jin Park, MD

Role: backup

References

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.

Reference Type: DERIVED

PMID: 32375688 (View on PubMed)

Other Identifiers

2018-0228

Identifier Type: -

Identifier Source: org_study_id