Ovarian cancer ctDNA Nir-Bev study

JRCT ID: jRCT2031220732

Registered date:25/03/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Ovarian cancer
• Date of first enrollment: 05/12/2023
• Target sample size: 70
• Study type: Interventional

Intervention(s)

Randomized after IDS and before the second or third cycle of TC therapy after IDS to either of the following treatments:
- 3 cycles of total TC therapy including before randomization (1 cycle is 21 days, paclitaxel: 175/180 mg/m^2 and carboplatin: AUC=5.0/6.0 intravenous infusion at day1). After that, maintenance therapy of daily oral administration of niraparib tablets at 200 mg/day or 300 mg/day for 3 years.
- 1 or 2 cycles TC + Bev therapy of total 3 cycles chemotherapy after IDS (1 cycle is 21 days, paclitaxel: 175/180 mg/m^2, carboplatin: AUC=5.0/6.0 and bevacizumab: 15 mg/kg intravenous infusion at day1).
After that, niraparib tablets will be taken orally at 200 mg/day or 300 mg/day for 3 consecutive years, and 16 cycles (1cycle is 21 days) of bevacizumab: 15 mg/kg intravenous infusion at day 1 will be administered.

Outcome(s)

• Primary Outcome: Progression free survival: PFS

Secondary Outcome

ctDNA negative conversion rate
Overall survival (OS)
Time to first subsequent treatment (TFST)
Adverse event rate
Treatment completion rate
Response rate (RR)
Disease control rate (DCR)
QOL

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Female

Include criteria

1. Participated in "Genetic Alterations and clinical record in surgically debulked OVarian cancer patients by Liquid biopsy And whole eXome analYsis: GALAXY-OV trial" with written consent.
2. Histopathologically diagnosed with primary ovarian cancer (including ovarian cancer, fallopian tube cancer, and peritoneal cancer).
3. 2014 FIGO classification stage III-IV
4. Interval debulking surgery (IDS) has been performed for primary and metastatic lesions.
5. Ovarian cancer tumor tissue or cell block was collected before neoadjuvant chemotherapy.
6. No more than 4 cycles of neoadjuvant chemotherapy.
7. Aged 18 years or older at the time of informed consent.
8. Oral intake is possible.
9. ctDNA positive in the SignateraTM analysis using postoperative blood specimens.
10. ECOG performance status (PS) of 0 or 1 at the time of informed consent for this study.
11. At the time of informed consent and screening test for this study, there is no severe damage to major organs (bone marrow, heart, lung, liver, kidney, etc.) and the following criteria are met. (Use the test results before the administration of postoperative chemotherapy immediately before registration. If there are no applicable laboratory test values, measure immediately before registration.)
- Neutrophil count >= 1,500/microliter
- platelet count >= 100,000/microliter
- hemoglobin >= 8.0 g/dL
- serum creatinine <= 1.5 * upper limit of normal (ULN)
- total bilirubin <= 1.5 * ULN
- ALT and AST <= 2.5 * ULN, <= 5 * ULN if liver metastases
12. Urine protein less than 2+ on urinalysis. If the urinalysis is 2+ or greater, the urinary protein/creatinine ratio is less than 1.
13. Normal blood pressure or appropriately treated and controlled hypertension (systolic BP 140 mmHg or less and/or diastolic BP 90 mmHg or less)
14.Written informed consent to participate in the study was obtained voluntarily after a full explanation of the study prior to enrollment in this study.

Exclude criteria

1.Patients with sarcoma or non-epithelial ovarian cancer.
2.Have a history of malignant tumors other than ovarian cancer.
Patients with a recurrence-free interval of 5 years or longer, or basal or squamous cell carcinoma of the skin, superficial bladder cancer, cervical cancer, carcinoma in situ (carcinoma in situ) judged to have been cured by topical treatment or patients with lesions equivalent to intramucosal carcinoma can be enrolled.
3. HBs antigen positive, HBc antibody positive, or HCV antibody positive.
4. HIV antibody positive (registration is possible even if HIV antibody has not been tested).
5.History of interstitial lung disease (interstitial pneumonia, pulmonary fibrosis, etc.) requiring treatment, or extensive findings of these on CT.
6. Poorly controlled comorbidities or active infections.
7. Receiving continuous systemic administration (oral or intravenous) of corticosteroids (prednisolone equivalent of at least 10 mg/day for at least 2 weeks).
8.Previous treatment with Poly(ADP-ribose) polymerase (PARP) inhibitors.
9.The patient is judged to have difficulty enrolling in this clinical trial due to a clinically problematic psychiatric disorder.
10.History of hemoptysis.
11.History of hypertensive crisis (CTCAE Grade 4) or hypertensive encephalopathy.
12.History of cerebrovascular disease, transient ischemic attack, subarachnoid hemorrhage or posterior reversible encephalopathy syndrome.
13. Has a history or signs of bleeding disorders.
14.Bleeding diathesis or signs of severe hematological disorder (no blood clotting).
15. History or clinical suspicion of brain metastasis or spinal cord compression. If brain metastasis is suspected, brain CT/MRI (within 4 weeks before enrollment) is mandatory. Spinal cord MRI (within 4 weeks prior to enrollment) is mandatory if spinal cord compression is suspected.
16. History of central nervous system disease or signs on neurological examination, except when adequately managed with standard therapy.
17. Patient with Intractable wound, active ulcer or fracture. Patients treated with open granulation tissue therapy for secondary healing and no signs of superficial wound dehiscence or infection are eligible but require wound evaluation every 3 weeks.
18. Concomitant clinically significant intestinal obstruction.
19. Physical examination or laboratory findings that are contraindications to the use of niraparib and bevacizumab or that are reasonably suspicious of disease or morbidity that increases the risk of treatment-related complications.
20. Pregnant or breastfeeding women.
21. Participation in other clinical trials is not permitted. (except for clinical trials, etc. that do not involve therapeutic intervention)
22. The attending physician determines that the patient is not suitable for enrollment in this clinical trial.

Related Information

• Primary Sponsor: Chiyoda Tatsuyuki
• Source(s) of Monetary Support: Takeda Pharmaceutical Co., Ltd.