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Efficacy and Safety of Niraparib Combined With Oral Etoposide in Platinum Resistant/Refractory Recurrent Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04217798
Recruitment Status : Not yet recruiting
First Posted : January 3, 2020
Last Update Posted : January 3, 2020
Sponsor:
Collaborator:
Zai Lab (Shanghai) Co., Ltd.
Information provided by (Responsible Party):
Peking Union Medical College Hospital

Brief Summary:
To evaluate the efficacy and safety of niraparib combined with oral etoposide in platinum resistant or platinum refractory recurrent ovarian cancer.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Niraparib Phase 2

Detailed Description:
This is a single arm, prospective, multicenter, phase II study to evaluate the efficacy and safety of PARP inhibitor niraparib combined with oral etoposide chemotherapy in women with platinum resistant or refractory recurrent ovarian cancer. Subjects will receive niraparib and oral etoposide in 30-day treatment cycles. After 6-8 cycles, oral etoposide will be discontinued. Subjects will receive niraparib alone until disease progression, intolerable toxicity or withdrawal of informed consent. The primary endpoint is efficacy as defined overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Secondary endpoints include progression free survival, duration of response, disease control rate, CA125 response rate and safety.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 35 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Prospective, Multicenter, Phase II Study to Evaluate the Efficacy and Safety of Niraparib Combined With Oral Etoposide in Platinum Resistant/ Refractory Recurrent Ovarian Cancer
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : January 1, 2022


Arm Intervention/treatment
Experimental: Niparib combined with oral etoposide
Subjects will receive niraparib 200mg/day in combination with oral etoposide (50 mg/ day, on day 1-20, every 30 days). After 6-8 cycles, oral etoposide will be discontinued. Subjects will receive niraparib alone until disease progression, intolerable toxicity or withdrawal of informed consent.
Drug: Niraparib
Subjects will receive niraparib combined with oral etoposide (on day 1-20, every 30 days). After 6-8 cycles, oral etoposide will be terminated. Niraparib will be still given to subjects until disease progression, intolerable toxicity or withdrawal of informed consent.
Other Name: oral etoposide




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Through study completion, an average of 1 year ]
    ORR is defined as the proportion of subjects who have a partial response (PR) or complete response (CR) to therapy according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Through study completion, an average of 1 year ]
    PFS is defined as the time from randomization to first disease progression by investigator assessment using RECIST 1.1 or death, from any cause, whichever comes first.

  2. Duration of Response (DOR) [ Time Frame: Through study completion, an average of 1 year ]
    DOR is defined as the time from the first date of response until the date of first documented progression.

  3. Disease Control Rate (DCR) [ Time Frame: Through study completion, an average of 1 year ]
    DCR is defined as the proportion of subjects who have a complete response (CR), partial response (PR) and stable disease (SD) to therapy according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  4. CA125 Response Rate [ Time Frame: Through study completion, an average of 1 year ]
    The proportion of subjects with a minimum 50% reduction in CA-125 serum levels lasting for ≥28 days relative to baseline CA-125 serum levels.

  5. The frequency and severity of adverse events [ Time Frame: Through study completion, an average of 1 year ]
    The frequency and severity of adverse events evaluated according to NCI CTCAE version 5.0 during subjects receiving the study treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent before undertaking any study procedure.
  • Female, age 18-70.
  • Histologically confirmed FIGO stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
  • No limitation of the BRCA mutation and HRD status.
  • Platinum resistant or refractory recurrent disease.
  • Subjects must have received at least 1 prior line of platinum-based chemotherapy regimen and no more than twice.
  • Subjects must have measurable lesions (according to RECIST1.1 criteria).
  • Subjects must have radiologically confirmed disease progression at the time of previous treatment; or CA125 elevated for two consecutive times and 2.5 times upper the limit of normal value.
  • Life expectancy of more than 6 months.
  • ECOG 0-1.
  • Good organ function, including:

    • Bone marrow function: neutrophil count ≥1,500/µL, platelets ≥100,000/µL, hemoglobin ≥10 g/dL;
    • Hepatic function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or direct bilirubin ≤1.0 x ULN, AST and ALT ≤2.5 x ULN unless liver metastases are present, in which case they must be ≤5 x ULN;
    • Renal function: serum creatinine ≤1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation.
  • Has a negative serum pregnancy test within 3 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 3 months after the last dose of study treatment, or is of non-childbearing potential. Non-childbearing potential is defined as follows (by other than medical reasons):

    • ≥45 years and <60 years of age and has not had menses for >1 year
    • ≥60 years of age
    • Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation.
  • Is able to adhere to the protocol.
  • Has recovered from previous chemotherapy induced toxic side effects to ≤ grade 1 CTCAE or basal level, apart from ≤ grade 2 CTCAE peripheral neuropathy or hair loss symptoms at steady state.

Exclusion Criteria:

  • Has a known hypersensitivity to the active or inactive ingredients of niraparib or compound which has similar chemical structure to niraparib.
  • Has a known hypersensitivity to the active or inactive ingredients of etoposide or compound which has similar chemical structure to etoposide.
  • prior PARP inhibitor therapy.
  • Has symptomatic uncontrolled brain or leptomeningeal metastasis.
  • Major surgery or chemotherapy within 3 weeks of starting the study or patient has not recovered from any effects of the surgery.
  • Receive palliative radiotherapy encompassing > 20% of the bone marrow within 1 week of entering the study.
  • Be diagnosed any invasive cancer other than ovarian cancer (apart from cured basal cell carcinoma and squamous cell carcinoma) within 2 years prior to study enrolment.
  • Previously or currently diagnosed of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
  • Has other serious or uncontrolled disease.
  • Has any disease, treatment and laboratory abnormality that may interfere the study results and affect the fully attendance of study. Or the subject is considered to be not suitable for the study by the investigator. Cannot receive platelet or red blood cell transfusion within 4 weeks of study drug administration.
  • Pregnant, breastfeeding or expecting to conceive children during the study treatment period.

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): NCT04217798


Contacts
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Contact: Jiaxin Yang, MD 13661160998 yangjiaxin@pumch.cn
Contact: HuiMei Zhou, MD 18600012090 mayflower0808@126.com

Sponsors and Collaborators
Peking Union Medical College Hospital
Zai Lab (Shanghai) Co., Ltd.

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Responsible Party: Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT04217798    
Other Study ID Numbers: CH1902001
First Posted: January 3, 2020    Key Record Dates
Last Update Posted: January 3, 2020
Last Verified: March 2019
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 Peking Union Medical College Hospital:
platinum resistent/refractory, ovarian cancer
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Etoposide
Etoposide phosphate
Niraparib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Poly(ADP-ribose) Polymerase Inhibitors