Timing of Surgery After Neoadjuvant Chemotherapy for Advanced Ovarian Cancer

Official title

Timing of Surgery After Neoadjuvant Chemotherapy for Advanced Ovarian Cancer: A Randomized Clinical Trial for Early Versus Delayed Interval Cytoreductive Surgery

Overview

Ovarian cancer is among the top five primary causes of cancer-related mortality in women. Most ovarian malignant tumours originate from epithelial cells The majority of patients typically have advanced-stage tumours at diagnosis. When complete surgery with no macroscopic visible disease is not feasible due to both the spread of the disease and the patient's general condition, neoadjuvant chemotherapy (NACT) of 3 cycles followed by interval cytoreductive surgery (ICS) or final cytoreductive surgery (FCS) after 6 cycles of NACT followed or not by adjuvant chemotherapy can be offered, with similar overall survival. In our centre, due to logistics, disease, or patient factors, many patients may receive more than 3 cycles of NACT before ICS. Therefore, this randomized controlled trial aims to evaluate the survival benefit of different timings of ICS after 3 or 6 cycles of NACT in patients not eligible for upfront cytoreductive surgery (UCS).

Interventions

• Procedure Delayed interval cytoreductive surgery (DICS)
  patients will receive six courses of intravenous carboplatin and paclitaxel every 3 weeks, followed by delayed interval cytoreductive surgery (DICS) within 6 weeks of the last cycle of chemotherapy. After DICS, patients will be assessed for the need or not for further adjuvant chemotherapy. chemotherapy regimen: * Paclitaxel at 175 mg/m² + carboplatin area under the curve (AUC) 5-6 every 3 weeks. * Paclitaxel at 60 mg/m² (days 1, 8, and 15), and carboplatin AUC 2 (days 1, 8, and 15) every 3 we
• Procedure Early interval cytoreductive surgery (EICS)
  patients will receive three courses of intravenous carboplatin and paclitaxel every 3 weeks, followed by early interval cytoreductive surgery (EICS) within 6 weeks of the last cycle of chemotherapy. After EICS, patients will receive adjuvant three courses of intravenous carboplatin and paclitaxel every 3 weeks, then will be assessed for the need or not for further adjuvant chemotherapy. chemotherapy regimen: * Paclitaxel at 175 mg/m² + carboplatin area under the curve (AUC) 5-6 every 3 weeks.

Primary outcome measures

• Progression-free survival (PFS) [Time frame: up to 5years]
• Overall survival (OS) [Time frame: up to 5 years]

Secondary outcome measures (7)

• Operative peritoneal cancer index (PCI) assessment [Time frame: 3-6 months]
• Complete resection rate [Time frame: 3-6 months]
• Surgical complexity scoring (low, intermediate, or high) [Time frame: 3-6 months]
• Post-operative morbidity [Time frame: within 30 days of surgery]
• Pathological complete chemotherapy response score (CRS 3) [Time frame: 3-6 months]
• The total number of chemotherapy cycles administered [Time frame: 8 months]
• Tumour recurrence and death [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

• Female Patients aged 18 to 75 years.
• International Federation of Gynecology and Obstetrics (FIGO) stage IIIB-IV unsuitable for UCS.
• Histologically confirmed high-grade serous (HGS) ovarian, fallopian tube, or primary peritoneal carcinoma.
• ECOG performance status: 0 or 1.
• Resectable disease by laparoscopic assessment after 3 cycles of NACT.
• Adequate haematology, bone marrow, respiratory, hepatic, cardiac and renal functions.
• Estimated life expectancy of > 3 months according to Age-adjusted Charlston Co-morbidity Index (ACCI), included patients should have a low or intermediate comorbidity score; ACCI 0-3.

Exclusion criteria

• Metastatic ovarian carcinoma.
• Patients with primary ovarian carcinoma other than high-grade serous (low-grade serous, endometrioid, mucinous, clear cell, and non-epithelial ovarian carcinoma).
• Presence of pregnancy or breast-feeding.
• History of other invasive malignancies in the previous 5 years.
• History of a recent < 6 month cerebrovascular accident.
• Uncontrolled systemic disease or contraindication to chemotherapy.
• Progressive disease on NACT.
• Worsening Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG 2-4).
• Severe comorbidities (ACCI >= 4)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Egypt · 1 center

• Elshatby Maternity University Hospital — Alexandria

Identifiers

NCT: NCT06404671 · SGOU 1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗