Timing of Surgery After Neoadjuvant Chemotherapy for Advanced Ovarian Cancer

Ovarian Epithelial Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06404671
• Other study ID #: SGOU 1
• Status: Recruiting
• Phase: N/A
• Start date: September 15, 2023
• Est. completion date: March 20, 2029

Study information

• Verified date: January 2024
• Source: Alexandria University
• Contact: Hayat Sharaf, MsC
• Phone: 00201025774942
• Email: h_mohammed14[@]alexmed.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: March 20, 2029
• Est. primary completion date: December 30, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Epithelial Cancer
• Ovarian Neoplasms

Intervention

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.
• 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.

Locations

Country	Name	City	State
Egypt	Elshatby Maternity University Hospital	Alexandria

Sponsors (1)

Lead Sponsor	Collaborator
Alexandria University

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Operative peritoneal cancer index (PCI) assessment	pre- and post-operative PCI	3-6 months
Secondary	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
Secondary	Surgical complexity scoring (low, intermediate, or high)	assessment of complexity score of during surgery	3-6 months
Secondary	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
Secondary	Pathological complete chemotherapy response score (CRS 3)	Pathological complete chemotherapy response score (CRS 3) in the pathology specimen	3-6 months
Secondary	The total number of chemotherapy cycles administered	The total number of chemotherapy cycles administered (NACT + adjuvant cycles).	8 months
Secondary	Tumour recurrence and death	Proportion of patients who had recurrence or died in each group.	Up to 5 years