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 Information
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
Administrative Informations
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