Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinoma
Conditions
Keywords
advanced, ovarian cancer, fallopian tube cancer, primary peritoneal cancer, neoadjuvant chemotherapy, interval debulking surgery, kelim
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. CA-125 ELIMination Rate Constant K (KELIM) will be determined using online tool. 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.
Interventions
DIAGNOSTIC_TESTKELIM
(i) Patients with KELIM =\>1 will receive radiological assessment and undergo internal debulking surgery if the disease is operable. (ii) 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
Neoadjuvant chemotherapy
PROCEDUREInterval debulking surgery
Interval debulking surgery
Sponsors
Queen Mary Hospital, Hong Kong
United Christian Hospital
Pamela Youde Nethersole Eastern Hospital
The University of Hong Kong-Shenzhen Hospital
Sun Yat-sen University Cancer Centre
The University of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Completeness of resection is assessed by independent surgeon
Intervention model description
non-inferiority randomised trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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 epithelial ovarian cancer (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 neoadjuvant chemotherapy (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 interval debulking surgery (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 homologous recombination deficiency (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 primary debulking surgery (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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 12-month progression-free survival (PFS) rate by RECIST criteria | up to 24 months from randomisation | PFS is defined as the time from the date of randomization until the date of progressive disease or death (whichever comes first). |
| Complete resection (CC0) rate | up to 24 weeks from randomisation | The likelihood of CC0 in patients who undergo IDS when KELIM reaches \>=1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) by RECIST criteria | up to 5 years from randomisation | PFS is defined as the time from the date of randomization until the date of progressive disease or death (whichever comes first). |
| Overall survival (OS) | Up to 5 years from randomisation | OS is defined as the time from the date of randomization until death due to any cause. |
| Quality-of-life scale | up to 1 year from randomisation | Different functional scales will be assessed by questionnaires like the EORTC questionnaires where all scales range from 0-100. The higher the score, the greater the intensity of that particular item is. |
| Incidence of adverse events | up to 1 year from randomisation | The complication rates of surgery based on the Clavien-Dindo classification and chemotherapy based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) |
| Chemotherapy response score (CRS) | up to 24 weeks from randomisation | CRS of omentum removed during interval debulking surgery CRS 1, there is no or minimal tumor response; CRS 2, there is appreciable tumor response amidst viable tumor; CRS 3, there is complete or near complete response with no residual tumor or minimal irregularly scattered tumor foci seen as individual cells, cell groups or nodules up to 2 mm |
Other
| Measure | Time frame | Description |
|---|---|---|
| Expression of biomarkers | up to 1 year from randomisation | Expression levels of biomarkers before and after chemotherapy |
Countries
China, Hong Kong
Contacts
Primary ContactLesley Lau, MPhil
Backup ContactIris Tang
Outcome results
None listed