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Niraparib Monotherapy as Maintain and Recurrent Treatment of Endometrial Serous Carcinoma

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ClinicalTrials.gov Identifier: NCT04716686
Recruitment Status : Recruiting
First Posted : January 20, 2021
Last Update Posted : January 20, 2021
Sponsor:
Collaborators:
Sun Yat-sen University
Tongji Hospital
Women's Hospital School Of Medicine Zhejiang University
Zai Lab (Shanghai) Co., Ltd.
Information provided by (Responsible Party):
Beihua Kong, Shandong University

Brief Summary:

Endometrial Serous carcinoma (ESC) has similar molecular characteristics to high-grade serous ovarian carcinoma (HGSOC) and basal cell-like breast cancer, such as similar Chromosomal instability, somatic copy number variation profiles and somatic mutations. The clinical treatment of ESC also refers to the treatment model of HGSOC. The PARP inhibitor niraparib used in this study, which was approved by FDA for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy on March 27, 2017.

The homologous recombination related gene mutations in total endometrial cancer accounted for 22%. Homologous Recombination Repair Defect (HRD) +ARID1A accounted for 48%, and 53% of endometrial cancer cell lines were sensitive to PARP inhibitors. The incidence of HRD in endometrial cancer with high copy number (the pathological type is mainly ESC) is 50%, suggesting potential clinical applications of PARP inhibitors for the treatment of ESC.


Condition or disease Intervention/treatment Phase
Endometrial Carcinoma Serous Carcinoma Drug: Niraparib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 83 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Niraparib Monotherapy as Maintain and Recurrent Treatment of Endometrial Serous Carcinoma: A Multi-center, Open-label, Prospective Clinical Study
Estimated Study Start Date : February 1, 2021
Estimated Primary Completion Date : July 30, 2023
Estimated Study Completion Date : July 30, 2023


Arm Intervention/treatment
Experimental: Niraparib as maintenance therapy for Endometrial Serous Carcinoma
For patients with baseline weight ≥ 77 kg and baseline platelets ≥ 150000/uL, a starting dose of 300 mg QD will be given; other patients will be given a starting dose of 200 mg QD. One treatment cycle is 28 days; follow-up and evaluation will be conducted every 2 cycles until the disease progression or patients cannot tolerate.
Drug: Niraparib
Patients received oral niraparib 200/300 mg QD and every cycle (28 days) thereafter until disease progression.

Experimental: Niraparib as recurrent therapy for Endometrial Carcinoma
For patients with baseline weight ≥ 77 kg and baseline platelets ≥ 150000/uL, a starting dose of 300 mg QD will be given; other patients will be given a starting dose of 200 mg QD. One treatment cycle is 28 days; follow-up and evaluation will be conducted every 2 cycles until the disease progression or patients cannot tolerate.
Drug: Niraparib
Patients received oral niraparib 200/300 mg QD and every cycle (28 days) thereafter until disease progression.




Primary Outcome Measures :
  1. PFS%(1 year) [ Time Frame: assessed up to 12 months ]
    for maintenance therapy arm

  2. Objective Response Rate (ORR) [ Time Frame: assessed up to 30months] ]
    for maintenance therapy arm


Secondary Outcome Measures :
  1. PFS%(2 year) [ Time Frame: assessed up to 24 months ]
    for maintenance therapy am

  2. Overall Survival (OS) [ Time Frame: assessed up to 30 months ]
    for maintenance therapy am

  3. Median PFS [ Time Frame: assessed up to 30 months ]
    for recurrent therapy am

  4. TEAEs [ Time Frame: assessed up to 30 months ]
    for maintain and recurrent therapy arms


Other Outcome Measures:
  1. PFS/ORR of Participants with BRCA+ or HRD+ [ Time Frame: assessed up to 30 months ]
    for maintain / recurrent therapy arms



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women aged 18 or above
  • Histological confirmation of serous endometrial cancer or other types of endometrial cancer
  • FIGO stage III-IV
  • ESC Patients have received at least 6 cycles of first-line platinum containing chemotherapy after surgery and achieved CR, PR or SD; ESC patients have received platinum containing chemotherapy after the first relapse and achieved CR, PR or SD; these two types of patients are enrolled in cohort 1 and receive niraparib alone as maintenance therapy within 12 weeks after the last chemotherapy treatment.
  • ESC Patients have received >2 lines of platinum containing chemotherapy and relapsed; patients with other types of endometrial cancer have received >2 lines of platinum containing chemotherapy and have BRCA mutation or be defined as HRD positive; these 2 types of patients are enrolled in cohort 2 and receive niraparib monotherapy.
  • Radiotherapy or endocrine therapy history is allowed
  • Cohort 1 life expectancy> 6 months; Cohort 2 life expectancy> 4 months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Patients agreed to provide blood samples for testing BRCA status and HRR mutations.
  • Patients agreed to provide formalin-fixed and paraffin-embedded tumor tissue samples for the detection of homologous recombination repair related genes (optional)
  • Laboratory criteria are as follows:
  • Neutrophil count ≥1500/µL;Platelets ≥100,000/µL;Hemoglobin ≥10g/dL;Serum creatinine ≤1.5 times of the upper limit, or creatinine clearance ≥60mL/min;Total bilirubin ≤1.5 times of the upper limit or direct bilirubin ≤1.0 times of the upper limit;AST and ALT ≤2.5 times of the upper limit, and must be ≤5 times of the upper limit of when liver metastasis exists.
  • Patients of reproductive potential must have a negative urinary or serum pregnancy test when done and promise to take effective contraceptive measuresduring the period of the study; Or without potential fertility, defined as:
  • Women who have undergone contraceptive operation(hysterectomy, bilateral oophorectomy or bilateral salpingectomy), or
  • over 60 years old, or≥40 and <60 years of age, menopause for more than 12 months, and follicle-stimulating hormone test results are within the reference range of research institutions after menopause
  • Willingness to sign a written informed consent document and follow the plan
  • Any previous toxic and side effects of chemotherapy have recovered to ≤ CTCAE level 1 or baseline level, except for sensory neuropathy or hair loss with stable symptoms ≤ CTCAE level 2

Exclusion Criteria:

  • Allergic to active or inactive ingredients of ZL-2306 (nirapali) or drugs with similar chemical structure to ZL-2306 (nirapali)
  • Stage Ia(on invasion to myometrium)
  • Symptomatic, uncontrollable brain metastases or pial metastases(No imaging scan is required); patients with spinal cord compression can still be considered for enrollment if they have received targeted therapy and have evidence of clinically SD for at least 28 days (patients with controlled central nervous system metastasis must have received radiotherapy or chemotherapy at least 1 month before and with no new symptoms related to central nervous system lesions or symptoms suggesting disease progression)
  • Received surgery within 3 weeks before the start of the study, or any surgical effects that have not recovered.
  • Received palliative radiotherapy with >20% bone marrow 1 week before enrollment
  • Suffered from other aggressive cancers (except for fully treated basal or squamous cell skin cancer) within 2 years before enrollment
  • Previously or currently diagnosed as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
  • Suffer from serious or uncontrollable diseases, including but not limited to:
  • Uncontrollable nausea and vomiting, inability to swallow drugs, any gastrointestinal diseases that may interfere with drug absorption and metabolism
  • Active viral infections such as human immunodeficiency virus, hepatitis B, hepatitis C, etc.
  • Uncontrolled grand mal seizures, unstable spinal cord compression, superior vena cava syndrome, or other mental disorders
  • Immune deficiency (except for splenectomy)
  • Any past or current disease, treatment or laboratory abnormality that may interfere with the results of the study, or be defined as not suitable for this study
  • Receive platelet or red blood cell transfusion within 4 weeks before the start of the study.
  • Pregnant or breastfeeding, or expect to become pregnant during the study.
  • Have received any PARP inhibitor treatment previously.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04716686


Contacts
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Contact: Qing Zhang 86-18560085996 qiluqingzhang@sdu.edu.cn

Locations
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China, Shandong
Qilu Hospital of Shandong University Recruiting
Jinan, Shandong, China, 250012
Contact: Xi Zhang    86-18560082013    happylittlebrook@163.com   
Sponsors and Collaborators
Shandong University
Sun Yat-sen University
Tongji Hospital
Women's Hospital School Of Medicine Zhejiang University
Zai Lab (Shanghai) Co., Ltd.
Additional Information:
Publications:

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Responsible Party: Beihua Kong, professor, Shandong University
ClinicalTrials.gov Identifier: NCT04716686    
Other Study ID Numbers: ZL-2306-914
First Posted: January 20, 2021    Key Record Dates
Last Update Posted: January 20, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Beihua Kong, Shandong University:
Endometrial Serous carcinoma
maintenance therapy
recurrent therapy
PARP inhibitor
Additional relevant MeSH terms:
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Carcinoma
Endometrial Neoplasms
Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Cystadenocarcinoma
Adenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents