Niraparib for the Neoadjuvant Treatment of Unresectable Ovarian Cancer

Study Overview
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Brief Summary
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This is a prospective, interventional, single-arm, open-label, phase II study to evaluate the safety and efficacy of niraparib monotherapy as neoadjuvant therapy in patients with advanced ovarian cancer, primary peritoneal cancer, fallopian tube cancer ((FIGO stage III or IV), who can not achieve R0 tumor reduction surgery after imaging evaluation or laparoscopic evaluation or can not tolerate surgery.

Official Title
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Niraparib for the Neoadjuvant Treatment of Unresectable Ovarian Cancer

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Niraparib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The informed consent form must be provided before any procedure of the trial, and the informed consent form shall be filed in the research center; Female patients aged between 18 and 75 years old; Patients received open surgery, laparoscopic surgery, or coarse needle aspiration biopsy and confirmed as high-grade serous or endometrioid ovarian cancer, peritoneal cancer, or fallopian tube cancer (hereinafter referred to as ovarian cancer). FIGO stage III-IV; BRCA1/2 gene mutation or HRD was confirmed by tissue or blood samples detected by the testing institution designated by the research center; Blood and tissue samples can be obtained before, during, and after treatment, and the subjects agree to submit the blood and tissue samples to the central laboratory for the expanded research purposes of the trial, including but not limited to: I. possible gene-related research. II. Possible tumor markers related studies; There is at least one lesion that can be measured by CT / MRI; The professional gynecological oncologists appointed by each center should judge the patients who can not achieve R0 tumor reduction or can not tolerate surgery, The criteria for failure to achieve R0 tumor reduction include but are not limited to: i. Fagotti score ≥ 8 [2]; II. When the laparoscopic evaluation method is difficult to implement, the upper abdominal CT Score ≥ 3 can be used [3]. The criteria for intolerance to surgery can be considered as follows: III. advanced age: age ≥ 80; IV. body mass index: BMI ≥ 40.0; v. A variety of chronic diseases; Vi. malnutrition or hypoproteinemia; VII. Moderate to massive ascites; VIII. Newly diagnosed venous thromboembolism; IX. physical status: ECOG > 2. The expected survival time was more than 12 weeks; The ECOG score was 0-2; Good organ function, including: i. Bone marrow function: neutrophil count ≥ 1500 / μ L; platelet ≥ 100000 / μ L; hemoglobin ≥ 10g / dl II. Liver function: total bilirubin ≤ 1.5 times of the upper limit of normal value or direct bilirubin ≤ 1.0 times of the upper limit of normal value; AST and alt ≤ 2.5 times of the upper limit of normal value; when liver metastasis exists, it must be ≤ 5 times of the upper limit of normal value III. renal function: serum creatinine ≤ 1.5 times the upper limit of normal value, or creatinine clearance rate ≥ 60ml / min (calculated according to Cockcroft Gault formula); For women with fertility potential, if blood test or urine pregnancy test is negative within one week before enrollment, effective contraceptive measures must be taken, such as physical barrier contraceptive method (condom) or complete abstinence. Oral, injectable or implantable hormonal contraceptives are not allowed. Or women without reproductive potential, defined as: i. Natural menopause and menopause for more than 1 year; II. Surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); III. serum follicle-stimulating hormone, luteinizing hormone, and plasma estradiol levels were within the menopausal criteria of the research center laboratory. Understand the trial process and have the ability to comply with the trial protocol for the trial duration, including any treatment, examination, inspection, follow-up, and questionnaire required for the completion of the experiment; The patients were willing to complete the questionnaire survey of quality of life during the trial treatment and follow-up, and agreed that the results of the questionnaire survey could be used in clinical research; The toxicity of any previous chemotherapy has returned to ≤ CTCAE 1 or baseline level, except for sensory neuropathy or alopecia with stable symptoms ≤ CTCAE grade 2. Exclusion Criteria: - The enrolled patients should not contain any of the following conditions: Personnel involved in the formulation or implementation of the research plan; Other clinical drug experiments participated in by using other experimental research drugs at the same time as the study; At the same time of this study, other neoadjuvant therapies for cancer should be used, including but not limited to chemotherapy, radiotherapy, immunotherapy, microbial therapy, traditional Chinese medicine treatment, and other experimental therapies; Those who are known to be allergic to niraparib or active or inactive components of drugs with a similar chemical structure to niraparib; Inability to swallow oral drugs and any gastrointestinal diseases that may interfere with the absorption and metabolism of the study drugs, such as uncontrollable nausea and vomiting, gastrointestinal obstruction or malabsorption; Have received any anti-cancer treatment for ovarian cancer; Have been treated with known or possible PARP inhibitors in the past; Symptomatic or uncontrolled brain metastases requiring simultaneous treatment, including but not limited to surgery, radiation and / or corticosteroids, or clinical manifestations of spinal cord compression; Major surgery was performed within 3 weeks before the start of the study or did not recover after the operation; The subjects had other malignant diseases in the past 3 years, except skin squamous cell carcinoma, basal-like carcinoma, breast intraductal carcinoma in situ, or cervical carcinoma in situ. The patient had a previous or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML); Patients with serious and uncontrollable diseases or the general situation of the subjects judged by the researchers to be unsuitable for joining the study, including but not limited to: active viral infection, such as human immunodeficiency virus, hepatitis B, hepatitis C, etc.; severe cardiovascular disease, uncontrollable ventricular arrhythmia, myocardial infarction in the last three months; uncontrollable epileptic grand mal seizure, no control Stable spinal cord compression, superior vena cava syndrome or other mental disorders that affect patients' informed consent; hypertension beyond drug control; immune deficiency (except splenectomy) or other diseases that researchers believe may expose patients to high-risk toxicity; and; Any medical history or existing clinical evidence indicates that there may be confusion of study results, interference with patients' compliance with the trial protocol throughout the study treatment period, or not in the best interests of patients; The patient received platelet or red blood cell transfusion within four weeks before the start of treatment of the study drug; Patients who are pregnant or breastfeeding, or who plan to become pregnant during the study treatment. Unsolved clinical toxicity (≥ grade 2, except alopecia, neuralgia, lymphopenia, and depigmentation of skin)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Niraparib group<br>Niraparib was used in patients with newly diagnosed ovarian cancer before any treatment. The daily dose (e.g. 200 mg is 2 capsules of 100 mg) should be strictly controlled according to the experimental design. | Drug: Niraparib<br>* Niraparib was used as 100mg capsules once a day since cycle 1 / day 1. The daily dose (e.g. 200 mg is 2 capsules of 100 mg) should be strictly controlled according to the experimental design. Patients should take medicine regularly every day under the guidance of doctors (the best in the morning). The patient must swallow all the capsules completely and do not chew the capsules. You may drink water or eat when taking medicine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection rate | the percentage of patients received R0 resection after Niraparib neoadjuvant treatment. | 3-month | 
| Overall Response Rate (ORR) After Neoadjuvant treatment | Overall Response Rate according to RECIST1.1 after Neoadjuvant treatment. ORR is defined as the proportion of participants achieving Complete Response (CR) or Partial Response (PR) as assessed by the investigator per RECIST (v.1.1). Per RECIST 1.1, CR is defined as the disappearance of all target lesions; PR is defined as at least a 30% decrease in the sum of diameters (SoD) of target lesions. | 3-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate | Disease control rate is defined as the proportion of participants achieving Complete Response (CR), Partial Response (PR) or Stable Disease (SD) according to RECIST1.1 and CA125 according to GCIC guidelines | 3-month | 
| Complete pathologic response rate | Complete pathologic response rate is measured according to Miller-Panye system. | 3-month | 
| Progression Free Survival (PFS) | PFS is defined as the time in months from the date of first study drug administration to the date of first documentation of progressive disease (PD) or death as assessed by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. | 3-year | 
| Overall survival (OS) | Overall survival. OS is defined as the time from the study enrollment to death due to any cause. | 5-year | 
| Quality of Life (QOL) measures using Functional Assessment of Cancer Therapy (FACT- ovarian cancer) | To evaluate quality of life (QOL) for the subjects undergoing this treatment, using validated tools. QOL will be assessed every 3 months during treatment course. [Functional Assessment of Cancer Therapy - Ovarian Cancer questionnaire (score range from 0 to 160. Higher scores represent better quality of life. | 5 years | 
| Patient report outcome, EQ-VAS | life quality assessment. EQ-VAS, EuroQol-visual analogue scales. Score range from 0 [worse outcome] to 10 [better outcome]). | 3 years | 
| Rate of treatment interruption and termination | The rate of treatment interruption and termination caused by patients' intolerance of treatment side effects and other reasons; | 5 years | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | To further describe safety and assess toxicities encountered with the use of the proposed treatment regimen in patients with stage III, all stage IV ovarian cancer. | 5 years | 
| Overall Response Rate (ORR) during niraparib maintain treatment | Overall Response Rate according to RECIST1.1 during niraparib maintain treatment. ORR is defined as the proportion of participants achieving Complete Response (CR) or Partial Response (PR) as assessed by the investigator per RECIST (v.1.1). Per RECIST 1.1, CR is defined as the disappearance of all target lesions; PR is defined as at least a 30% decrease in the sum of diameters (SoD) of target lesions. | 1 year |