ICRA Randomised Controlled Trial

NCT ID: NCT07068464

Last Updated: 2025-07-16

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 682 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2034-01-31

Brief Summary

The standard of care for advanced stage epithelial ovarian cancer is primary cytoreduction surgery with the aim of complete cytoreduction, followed by platinum and taxane-based chemotherapy and consideration of maintenance therapy (bevacizumab or Poly ADP-ribose polymerase (PARP)-inhibitor). Neoadjuvant chemotherapy before and after interval cytoreduction surgery has become an alternative approach as randomized controlled trials have demonstrated non-inferiority of this type of management over primary surgery. In these studies, neoadjuvant chemotherapy was restricted to three to four cycles. However, real-world clinical practice varies, with centres giving more than four pre-operative cycles. The decision to delay surgery is complex and influenced by multiple factors. These include poor performance status, radiological evidence of unresectable sites of disease, or insufficient surgical resources (either lack of surgical expertise operating room availability due to waiting lists) particularly when high complexity surgery is required to achieve complete cytoreduction. International disparities in access to surgical resources between high and low-middle income country settings also results in delays to surgery.

Knowledge gap:

There is a paucity of data in the setting of extended use of neoadjuvant chemotherapy (more than four cycles). Data on the role of delayed cytoreduction surgery post four cycles are controversial. While some data have shown survival to be similar to that of patients undergoing interval cytoreductive surgery after three cycles,6-12 others have reported poorer prognosis. Conflicting data are due to selection biases such as heterogeneous inclusion criteria, small sample sizes and retrospective study designs. Delaying surgery to after four cycles has the potential to reduce surgical complexity and post-operative morbidity, and increase rates of complete cytoreduction (an independent marker of survival).

Our multi-centre, international, retrospective cohort study (GO SOAR2) of 2498 women from twenty-two centres across twelve countries with advanced stage ovary cancer, showed that interval cytoreduction surgery was associated with statistically significant greater overall survival in comparison to delayed cytoreduction surgery (HR 0.81, p=0.01) but was associated with a higher GO SOAR surgical complexity score and greater surgical morbidity. Our results indicate that early maximum effort cytoreduction surgery with complete cytoreduction in high volume centres with appropriate surgical skill mix and resources, is what is needed to increase overall survival for women with advanced stage ovarian cancer.

We present the study design for a pragmatic phase III superiority randomised controlled trial comparing overall survival following interval and delayed cytoreductive surgery.

Our hypothesis is that overall survival is greater following interval cytoreduction surgery when compared to delayed cytoreduction in women with stage III-IV epithelial ovarian cancer.

Conditions

Ovary Cancer

Study Design

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

Study Groups

interval cytoreduction surgery

interval cytoreduction surgery is defined as surgery after 3 cycles of carboplatin and paclitaxel neoadjuvant chemotherapy

Group Type: ACTIVE_COMPARATOR

interval cytoreduction surgery

Intervention Type: PROCEDURE

Interval cytoreduction surgery is defined as cytoreduction surgery after three cycles of carboplatin-paclitaxel neoadjuvant chemotherapy.

delayed cytoreduction surgery

delayed cytoreduction surgery is defined as surgery after 6 cycles of carboplatin and paclitaxel neoadjuvant chemotherapy

Group Type: EXPERIMENTAL

delayed cytoreduction surgery

Intervention Type: PROCEDURE

Delayed cytoreduction surgery is defined as cytoreduction surgery after six cycles of carboplatin and paclitaxel neoadjuvant chemotherapy.

Interventions

delayed cytoreduction surgery

Delayed cytoreduction surgery is defined as cytoreduction surgery after six cycles of carboplatin and paclitaxel neoadjuvant chemotherapy.

Intervention Type: PROCEDURE

interval cytoreduction surgery

Interval cytoreduction surgery is defined as cytoreduction surgery after three cycles of carboplatin-paclitaxel neoadjuvant chemotherapy.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Women ≥18 years of age.

2. Histologically confirmed high grade, serous, or endometrioid ovarian cancer, fallopian tube carcinoma, or primary peritoneal carcinoma.

3. International Federation of Gynecologic Oncology (FIGO) 2014 stage IIIA-IVB unsuitable for complete primary cytoreductive surgery because disease unresectable. Assessment of unresectable disease must have been made by staging CT chest abdomen pelvis +/- diagnostic laparoscopy.

4. Disease must be deemed resectable after three courses of neoadjuvant chemotherapy.

5. Patient must be fit for cytoreduction surgery and chemotherapy.

Exclusion Criteria

1. Women undergoing primary and recurrent cytoreductive surgery.

2. Mucinous, clear cell, carcinosarcoma, low-grade serous carcinoma, germ cell and sex cord stromal histopathologies.

3. Synchronous malignancies.

4. Unfit for surgery and or chemotherapy.

5. Pregnant or breastfeeding women.

6. Delivery of HIPEC at cytoreduction surgery.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

NHS Grampian

OTHER_GOV

Sponsor Role: lead

Responsible Party

Faiza Gaba

Dr

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Countries

United Kingdom

Central Contacts

Faiza Gaba

Role: CONTACT

faiza.gaba1@abdn.ac.uk

+442034567890

Facility Contacts

Faiza Gaba

Role: primary

faiza.gaba1@abdn.ac.uk

+442034567890

Other Identifiers

vF_ICRA

Identifier Type: -

Identifier Source: org_study_id