Timing of Surgery After Neoadjuvant Chemotherapy for Advanced Ovarian Cancer

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

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).

Study Overview

• Status: Recruiting
• Conditions: Ovarian Epithelial Cancer
• Intervention / Treatment: Procedure: Delayed interval cytoreductive surgery (DICS); Procedure: Early interval cytoreductive surgery (EICS)

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hayat Sharaf, MsC; Phone Number: 00201025774942; Email: h_mohammed14@alexmed.edu.eg
• Study Contact Backup: Name: Alaa Elzarkaa, PhD; Phone Number: 00201008296264; Email: A_elzarka09@alexmed.edu.eg

Study Locations

• Egypt
  • Alexandria, Egypt
    • Recruiting
    • Elshatby Maternity University Hospital
    • Contact: Mervat Elsersy, PhD; Phone Number: +20 109 6311548; Email: mervat.elsersy@alexmed.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female Patients aged 18 to 75 years.
2. International Federation of Gynecology and Obstetrics (FIGO) stage IIIB-IV unsuitable for UCS.
3. Histologically confirmed high-grade serous (HGS) ovarian, fallopian tube, or primary peritoneal carcinoma.
4. ECOG performance status: 0 or 1.
5. Resectable disease by laparoscopic assessment after 3 cycles of NACT.
6. Adequate haematology, bone marrow, respiratory, hepatic, cardiac and renal functions.
7. 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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: delayed interval cytoreduction surgery (DICS); delayed interval cytoreduction surgery after six courses of intravenous carboplatin and paclitaxel every 3 weeks	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 weeks.; Paclitaxel at dense dose 80 mg/m² (days 1, 8, and 15) and carboplatin AUC 5-6 (day 1) every 3 weeks.
Active Comparator: Early interval cytoreduction surgery (EICS); Early interval cytoreduction surgery after three courses of intravenous carboplatin and paclitaxel every 3 weeks	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.; Paclitaxel at 60 mg/m² (days 1, 8, and 15), and carboplatin AUC 2 (days 1, 8, and 15) every 3 weeks.; Paclitaxel at dense dose 80 mg/m² (days 1, 8, and 15) and carboplatin AUC 5-6 (day 1) every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS will be defined as the time to recurrence/progression, or the date of death. Disease recurrence/ progression is defined as an increase in cancer antigen 125 (CA 125) levels or evidence of recurrence by imaging and/or histology.	up to 5years
Overall survival (OS)	OS will be defined as the time until the patient's death from any cause. The time to event occurrence will be calculated from the time of randomization until the event of interest.	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Operative peritoneal cancer index (PCI) assessment	pre- and post-operative PCI	3-6 months
Complete resection rate	proportion of patients without macroscopically visible disease according to residual (R), patients will have R0 if no macroscopic residual, R1 if the residual is ≤10 mm, and R2 if the residual is > 10 mm.	3-6 months
Surgical complexity scoring (low, intermediate, or high)	assessment of complexity score of during surgery	3-6 months
Post-operative morbidity	Post-operative morbidity according to the Clavien-Dindo classification (CDC), i.e., proportion of severe complications (CDC grade 3-5) within 30 days of surgery.	within 30 days of surgery
Pathological complete chemotherapy response score (CRS 3)	Pathological complete chemotherapy response score (CRS 3) in the pathology specimen	3-6 months
The total number of chemotherapy cycles administered	The total number of chemotherapy cycles administered (NACT + adjuvant cycles).	8 months
Tumour recurrence and death	Proportion of patients who had recurrence or died in each group.	Up to 5 years

Collaborators and Investigators

• Sponsor: Alexandria University

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2023
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): March 20, 2029

Study Registration Dates

• First Submitted: May 1, 2024
• First Submitted That Met QC Criteria: May 4, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 4, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: high grade serous; advanced primary ovarian cancer; interval cytoreduction
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: SGOU 1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No