Niraparib for the Neoadjuvant Treatment of Unresectable Ovarian Cancer

NCT04507841 | Active Not Recruiting Phase 2

• 1 other identifier: 2019-TJ-OVNN
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

Brief Summary

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 had low likelihood of achieving R0 cytoreduction by imaging assessment or laparoscopic evaluation, or cannot tolerate PDS by poor conditions.

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Disease Control Rate

  3-month

• Complete pathologic response rate

  3-month

• Progression Free Survival (PFS)

  3-year

• Overall survival (OS)

  5-year

• Quality of Life (QOL) measures using Functional Assessment of Cancer Therapy (FACT- ovarian cancer)

  5 years

Study Arms (1)

Niraparib group

EXPERIMENTAL

Niraparib was used in patients with newly diagnosed ovarian cancer before any treatment with an individualized starting dose of 200mg/day or 300mg/day based on body weight or platelet count.

Drug: Niraparib

Interventions

Niraparib DRUG

Neoadjuvant niraparib monotherapy with an individualized starting dose of 200mg/day or 300mg/day based on body weight or platelet count. The 28-day treatment cycle consists of 21 days of medication followed by a 7-day break. Two cycles of neoadjuvant niraparib monotherapy were used, and the investigator may choose to have an additional cycle based on the patient's condition.

Niraparib group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Tongji Hospital: lead
• West China Second University Hospital: collaborator
• Qilu Hospital of Shandong University: collaborator
• Renmin Hospital of Wuhan University: collaborator
• Sun Yat-sen University Cancer Center, Sun Yat-sen University: collaborator
• Guangdong Provincial People's Hospital Affiliated to Southern Medical University: collaborator

Study Sites (1)

Tongji Hospital

Wuhan, Hubei, 430000, China

Location

Related Publications (6)

• Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Madry R, Christensen RD, Berek JS, Dorum A, Tinker AV, du Bois A, Gonzalez-Martin A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016 Dec 1;375(22):2154-2164. doi: 10.1056/NEJMoa1611310. Epub 2016 Oct 7.

  PMID: 27717299 BACKGROUND

• Gonzalez-Martin A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Perez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. doi: 10.1056/NEJMoa1910962. Epub 2019 Sep 28.

  PMID: 31562799 BACKGROUND

• Berek JS, Matulonis UA, Peen U, Ghatage P, Mahner S, Redondo A, Lesoin A, Colombo N, Vergote I, Rosengarten O, Ledermann J, Pineda M, Ellard S, Sehouli J, Gonzalez-Martin A, Berton-Rigaud D, Madry R, Reinthaller A, Hazard S, Guo W, Mirza MR. Safety and dose modification for patients receiving niraparib. Ann Oncol. 2018 Aug 1;29(8):1784-1792. doi: 10.1093/annonc/mdy181.

  PMID: 29767688 BACKGROUND

• Mirza MR, Avall Lundqvist E, Birrer MJ, dePont Christensen R, Nyvang GB, Malander S, Anttila M, Werner TL, Lund B, Lindahl G, Hietanen S, Peen U, Dimoula M, Roed H, Or Knudsen A, Staff S, Krog Vistisen A, Bjorge L, Maenpaa JU; AVANOVA investigators. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. Lancet Oncol. 2019 Oct;20(10):1409-1419. doi: 10.1016/S1470-2045(19)30515-7. Epub 2019 Aug 29.

  PMID: 31474354 BACKGROUND

• Xia Y, Huang P, Qian YY, Wang Z, Jin N, Li X, Pan W, Wang SY, Jin P, Drokow EK, Li X, Zhang Q, Zhang Z, Li P, Fang Y, Yang XP, Han Z, Gao QL. PARP inhibitors enhance antitumor immune responses by triggering pyroptosis via TNF-caspase 8-GSDMD/E axis in ovarian cancer. J Immunother Cancer. 2024 Oct 4;12(10):e009032. doi: 10.1136/jitc-2024-009032.

  PMID: 39366751 DERIVED

• Zhou D, Liu J, Liu R, Li H, Huang Y, Ma D, Hong L, Gao Q. Effectiveness and Safety of Niraparib as Neoadjuvant Therapy in Advanced Ovarian Cancer With Homologous Recombination Deficiency (NANT): Study Protocol for a Prospective, Multicenter, Exploratory, Phase 2, Single-Arm Study. Front Oncol. 2022 Mar 23;12:852772. doi: 10.3389/fonc.2022.852772. eCollection 2022.

  PMID: 35402241 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

niraparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Qinglei Gao, MD. PhD

  Tongji Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: August 11, 2020
• Study Start: January 8, 2021
• Primary Completion: September 25, 2023
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 17, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)