Clinical trial NCT07023484: Personalized Timing of Interval Debulking Surgery Based on KELIM After Neoadjuvant Chemotherapy in Advanced Ovarian Cancer - a Multicenter Randomized Phase II Non-inferiority Trial
Official title: Personalized Timing of Interval Debulking Surgery Based on KELIM After Neoadjuvant Chemotherapy in Advanced Ovarian Cancer - a Multicenter Randomized Phase II Non-inferiority Trial (PRESELECT-I Trial)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Keywords: advanced
ovarian cancer
fallopian tube cancer
primary peritoneal cancer
neoadjuvant chemotherapy
interval debulking surgery
kelim
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Queen Mary Hospital, Hong Kong
name: United Christian Hospital
name: Pamela Youde Nethersole Eastern Hospital
name: The University of Hong Kong-Shenzhen Hospital
name: Sun Yat-sen University Cancer Centre
First posted: 2025-06-17
Enrollment: 126
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: non-inferiority randomised trial
Primary purpose: TREATMENT

Brief summary: About 70% of epithelial ovarian cancer patients are diagnosed at advanced stage. When primary optimal surgery is not possible, neoadjuvant chemotherapy will followed by interval debulking surgery is one treatment option. However, there is no consensus on the optimal timing of the surgery. CA125 is a well-known tumor marker in ovarian cancer. Its kinetic change has been proven to correlate with the patients' response to chemotherapy and chance of optimal resection. This study aims to utilize the kinetic change of CA125 to customize the timing of surgery for individual patients and compare this with the standard clinical practice.

Detailed description: Recruited patients will be randomised into two groups. The control group will receive treatment according to the standard clinical practice. The investigation group will have an additional CA125 at the 5th week after the first cycle of chemotherapy. KELIM will be determined. Patients with KELIM =\>1 will receive radiological assessment and undergo internal debulking surgery if the disease is operable. Patients with KELIM \<1 will have alternative management, such as addition of bevacizumab or changing to dose-dense chemotherapy, and defer the interval debulking surgery.

Eligibility criteria: Inclusion Criteria:

1. Patients aged 18 years old or older
2. Patients with Eastern Cooperative Oncology Group score 0-1 within 28 days prior to recruitment
3. Patients who can sign the informed consent
4. Patients with stage III-IV histologically or cytologically confirmed EOC, fallopian tube or primary peritoneal cancer not amenable for PDS
5. Patients who have baseline computed tomography (CT) of thorax, abdomen and pelvis.
6. Patients who are planned for NACT using 3-weekly carboplatin and paclitaxel. Those who have received one cycle of NACT may be eligible if the CA125 schedule of the study group can be matched.
7. Patients who have an evaluable CA125 level at baseline (i.e., baseline level is at least 2x upper limit of normal)
8. Patients who agree for chemotherapy and IDS if the disease becomes operable after NACT
9. Patients with adequate hematologic, liver and renal functions for chemotherapy
10. Patients who agree to receive adjuvant chemotherapy after IDS. The total number of NACT and adjuvant chemotherapy should be four or above, up to maximum of 9 cycles.
11. Patients who have childbearing potential should practice highly effective contraception throughout the study until at least 30 days after completion of the treatment.
12. Patients must have either germline and / or somatic BRCA test, or HRD test.

Exclusion Criteria:

1. Patients who have borderline malignancy, or non-EOC like germ cell or sex cord tumor, or metastatic diseases from other origins
2. Patients with mucinous and neuroendocrine histology
3. Patients with history of other malignancies within five years
4. Patients who are eligible for PDS
5. Patients who cannot undergo PDS because of parametrial and/or vaginal involvement alone
6. Patients who are not fit for PDS because of medical morbidities or refusal of operation
7. Patients who have already started NACT outside the study centers, except those who have received only one cycle within 7 days and the baseline CA125 value within 3 days of NACT (normal cut-off 35 U/ml) is available
8. Patients who participate in other interventional studies
9. Patients who are pregnant or breastfeeding
10. Patients who have contraindications to platinum-based chemotherapy
11. Patents with active tuberculosis, history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) are excluded.

Primary outcomes:
measure: Complete resection (CC0) rate
timeFrame: up to 24 weeks from randomisation
measure: 12-month progression-free survival rate by RECIST criteria
timeFrame: up to 24 months from randomisation
Secondary outcomes:
measure: Chemotherapy response score
timeFrame: up to 24 weeks from randomisation
measure: Progression-free survival by RECIST criteria
timeFrame: up to 5 years from randomisation
measure: Overall survival
timeFrame: Up to 5 years from randomisation
measure: Incidence of adverse events
timeFrame: up to 1 year from randomisation
measure: Quality-of-life scale
timeFrame: up to 1 year from randomisation
Other outcomes:
measure: Expression of biomarkers
timeFrame: up to 1 year from randomisation
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
city: Shenzhen
country: China
facility: The University of Hong Kong - Shenzhen Hospital
city: Chai Wan
country: Hong Kong
facility: Pamela Youde Nethersole Eastern HospitalPamela Y
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital, Department of Clinical Oncology
city: Hong Kong
country: Hong Kong
facility: The University of Hong Kong, Department of Obstetrics and Gynaecology
city: Kwun Tong
country: Hong Kong
facility: United Christian Hospital
Study officials:
affiliation: The University of Hong Kong
name: Ka Yu Tse, MBBS, MMedSc, PhD, FRCOG
role: PRINCIPAL_INVESTIGATOR
References:
citation: Colomban O, Tod M, Peron J, Perren TJ, Leary A, Cook AD, Sajous C, Freyer G, You B. Bevacizumab for Newly Diagnosed Ovarian Cancers: Best Candidates Among High-Risk Disease Patients (ICON-7). JNCI Cancer Spectr. 2020 Apr 4;4(3):pkaa026. doi: 10.1093/jncics/pkaa026. eCollection 2020 Jun.
citation: Ducoulombier S, Golfier F, Colomban O, Benayoun D, Bolze PA, Tod M, You B. Modeling CA-125 During Neoadjuvant Chemotherapy for Predicting Optimal Cytoreduction and Relapse Risk in Ovarian Cancer. Anticancer Res. 2017 Dec;37(12):6879-6886. doi: 10.21873/anticanres.12150.
citation: You B, Colomban O, Heywood M, Lee C, Davy M, Reed N, Pignata S, Varsellona N, Emons G, Rehman K, Steffensen KD, Reinthaller A, Pujade-Lauraine E, Oza A. The strong prognostic value of KELIM, a model-based parameter from CA 125 kinetics in ovarian cancer: data from CALYPSO trial (a GINECO-GCIG study). Gynecol Oncol. 2013 Aug;130(2):289-94. doi: 10.1016/j.ygyno.2013.05.013. Epub 2013 May 18.
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citation: Thomas QD, Boussere A, Classe JM, Pomel C, Costaz H, Rodrigues M, Ray-Coquard I, Gladieff L, Rouzier R, Rouge TM, Gouy S, Barranger E, Sabatier R, Floquet A, Marchal F, Guillemet C, Polivka V, Martin AL, Colombo PE, Fiteni F. Optimal timing of interval debulking surgery for advanced epithelial ovarian cancer: A retrospective study from the ESME national cohort. Gynecol Oncol. 2022 Oct;167(1):11-21. doi: 10.1016/j.ygyno.2022.08.005. Epub 2022 Aug 13.