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Niraparib and Bevacizumab Maintenance Therapy in Platinum-sensitive Recurrent Ovarian Cancer Patients Previously Treated With a PARP Inhibitor (NIRVANA-R)

Primary Purpose

Platinum-sensitive Recurrent Ovarian Cancer Patients Previously Treated With a PARP Inhibitor

Status
Recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Niraparib-Bevacizumab
Sponsored by
Yonsei University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Platinum-sensitive Recurrent Ovarian Cancer Patients Previously Treated With a PARP Inhibitor focused on measuring ovarian cancer, Platinum-sensitive, PARP inhibitor

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Participant has histologically confirmed diagnosis of high-grade predominantly serous, endometrioid, carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous OC, primary peritoneal cancer, or fallopian tube cancer will be enrolled in this study (only up to 4 patients with clear cell carcinoma will be included and mucinous carcinoma will not be included).
  2. Participant has received at least 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 12 months' period between penultimate platinum regimen and progression of disease) Note: The last platinum regimen does not necessarily have to immediately follow the next to last (penultimate) platinum regimen. For example, if a patient received a non-platinum regimen between the penultimate platinum regimen and last platinum regimen, they could be eligible, so long as they meet all entry criteria.
  3. Participant has responded to last the platinum regimen (complete or partial response), remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen
  4. Participant had prior treatment with PARP inhibitor
  5. Participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA 1/2 and PD-L1 status prior to enrollment
  6. Female participants who are at least 20 years of age on the day of signing informed consent with
  7. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to enrollment.

    Female participants:

  8. A female participant is eligible to participate if she is not pregnant (see Appendix 2), not breastfeeding, and at least one of the following conditions applies:

    1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR
    2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days following the last dose of niraparib and at least 210 days following the last dose of chemotherapy or bevacizumab.

    Informed Consent

  9. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. The participant may also provide consent for future biomedical research; however, the participant may participate in the main study without participating in future biomedical research.
  10. Participant has adequate organ function as defined in the following contents; all screening laboratory tests should be performed within 10 days prior to the start of study treatment.

    • Absolute neutrophil count (ANC) ≥1500/µL
    • Platelets ≥100 000/µL
    • Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
    • Creatinine OR Measured or calculated creatinine clearance(GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
    • Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
    • AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
    • International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria:

  1. Participant has mucinous, germ cell, or borderline tumor of the ovary.
  2. Participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis
  3. Participant either has myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or has features suggestive of MDS/AML.
  4. Participant has a known additional malignancy that is progressing or has required active treatment within the past 2 years.

    Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ, endometrial carinoma) that have undergone potentially curative therapy are not excluded.

    Note: Participants with synchronous primary endometrial cancer or a past history of primary endometrial cancer that met the following conditions are not excluded: Stage not greater than IA: no more than superficial myometrial invasion.

  5. Drainage of ascites during last 2 cycles of last chemotherapy.
  6. Palliative radiotherapy within 1 week encompassing >20% of the bone marrow.
  7. Persistent > grade 2 toxicity from prior cancer therapy.
  8. Symptomatic uncontrolled brain or leptomeningeal metastases. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression may be considered if they have received definitive treatment for this and evidence of clinically stable disease for 28 days.
  9. Known hypersensitivity to the components of niraparib.
  10. Major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery.
  11. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent.
  12. History or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study treatment, or is not in the best interest of the patient to participate.
  13. Immunocompromised patients.
  14. Patients with known active hepatic disease (i.e. , Hepatitis B or C).

Sites / Locations

  • Yonsei University College of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

experimental

Arm Description

Platinum-sensitive recurrent ovarian cancer patients previously treated with a PARP inhibitor, Non-mucinous

Outcomes

Primary Outcome Measures

progression-free survival(6 months PFS rate)
To determine the clinical effectiveness of the study treatment assessed using progression free survival(6months) according to RECIST v1.1 criteria (Investigator determined)

Secondary Outcome Measures

Overall survival (OS)
Time to tumour progression (TTP)
Time to first subsequent treatment(or death)
Time to second subsequent treatment
progression-free survival

Full Information

First Posted
January 28, 2021
Last Updated
July 6, 2021
Sponsor
Yonsei University
Collaborators
Takeda
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1. Study Identification

Unique Protocol Identification Number
NCT04734665
Brief Title
Niraparib and Bevacizumab Maintenance Therapy in Platinum-sensitive Recurrent Ovarian Cancer Patients Previously Treated With a PARP Inhibitor
Acronym
NIRVANA-R
Official Title
A Single-arm Phase II Study of Niraparib and Bevacizumab Maintenance Therapy in Platinum-sensitive Recurrent Ovarian Cancer Patients Previously Treated With a PARP Inhibitor
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Recruiting
Study Start Date
July 5, 2021 (Actual)
Primary Completion Date
March 31, 2023 (Anticipated)
Study Completion Date
March 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yonsei University
Collaborators
Takeda

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is phase II, open label, clinical trial to determine the efficacy of Niraparib re-treatment with Bevacizumab of assessment progression-free survival(6 months PFS rate) with platinum-sensitive recurrent ovarian cancer patients previously treated with a PARP inhibitor.
Detailed Description
This is a Phase II, open-label, non-randomized, multi-center study assessing the efficacy and safety of Niraparib re-treatment with Bevacizumab of assessment progression-free survival(6 months PFS rate) with platinum-sensitive recurrent ovarian cancer patients previously treated with a PARP inhibitor The study will assess the effectiveness of progression-free survival(6 months PFS rate) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The subject will be treated to until disease progression as below: Niraparib 200mg or 300mg (once daily[QD])* Bevacizumab 15mg/kg every 3 weeks (Q3W) The recommended starting dosage of niraparib is 200mg QD. For patients who weigh ≥77 kg and have baseline platelet count ≥150,000/μL, the recommended starting dosage is 300 mg QD.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Platinum-sensitive Recurrent Ovarian Cancer Patients Previously Treated With a PARP Inhibitor
Keywords
ovarian cancer, Platinum-sensitive, PARP inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
experimental
Arm Type
Experimental
Arm Description
Platinum-sensitive recurrent ovarian cancer patients previously treated with a PARP inhibitor, Non-mucinous
Intervention Type
Drug
Intervention Name(s)
Niraparib-Bevacizumab
Intervention Description
Niraparib 200mg or 300mg (once daily[QD]) Bevacizumab 15mg/kg every 3 weeks (Q3W) *The recommended starting dosage of niraparib is 200mg QD. For patients who weigh ≥77 kg and have baseline platelet count ≥150,000/μL, the recommended starting dosage is 300 mg QD.
Primary Outcome Measure Information:
Title
progression-free survival(6 months PFS rate)
Description
To determine the clinical effectiveness of the study treatment assessed using progression free survival(6months) according to RECIST v1.1 criteria (Investigator determined)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Time Frame
Up to 1year
Title
Time to tumour progression (TTP)
Time Frame
Up to 1year
Title
Time to first subsequent treatment(or death)
Time Frame
The date of first documented first subsequent treatment or date of death, assessed up to 36months
Title
Time to second subsequent treatment
Time Frame
The date of first documented second subsequent treatment assessed up to 36months
Title
progression-free survival
Time Frame
Up to 1year

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Female
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participant has histologically confirmed diagnosis of high-grade predominantly serous, endometrioid, carcinosarcoma, mixed mullerian with high-grade serous component, clear cell, or low-grade serous OC, primary peritoneal cancer, or fallopian tube cancer will be enrolled in this study (only up to 4 patients with clear cell carcinoma will be included and mucinous carcinoma will not be included). Participant has received at least 2 previous courses of platinum-containing therapy, and has disease that was considered platinum sensitive following the penultimate (next to last) platinum course (more than 12 months' period between penultimate platinum regimen and progression of disease) Note: The last platinum regimen does not necessarily have to immediately follow the next to last (penultimate) platinum regimen. For example, if a patient received a non-platinum regimen between the penultimate platinum regimen and last platinum regimen, they could be eligible, so long as they meet all entry criteria. Participant has responded to last the platinum regimen (complete or partial response), remains in response and is enrolled on study within 8 weeks of completion of the last platinum regimen Participant had prior treatment with PARP inhibitor Participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion for prospective testing of BRCA 1/2 and PD-L1 status prior to enrollment Female participants who are at least 20 years of age on the day of signing informed consent with Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to enrollment. Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 2), not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days following the last dose of niraparib and at least 210 days following the last dose of chemotherapy or bevacizumab. Informed Consent The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. The participant may also provide consent for future biomedical research; however, the participant may participate in the main study without participating in future biomedical research. Participant has adequate organ function as defined in the following contents; all screening laboratory tests should be performed within 10 days prior to the start of study treatment. Absolute neutrophil count (ANC) ≥1500/µL Platelets ≥100 000/µL Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Creatinine OR Measured or calculated creatinine clearance(GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants Exclusion Criteria: Participant has mucinous, germ cell, or borderline tumor of the ovary. Participant has a history of non-infectious pneumonitis that required treatment with steroids or currently has pneumonitis Participant either has myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML) or has features suggestive of MDS/AML. Participant has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ, endometrial carinoma) that have undergone potentially curative therapy are not excluded. Note: Participants with synchronous primary endometrial cancer or a past history of primary endometrial cancer that met the following conditions are not excluded: Stage not greater than IA: no more than superficial myometrial invasion. Drainage of ascites during last 2 cycles of last chemotherapy. Palliative radiotherapy within 1 week encompassing >20% of the bone marrow. Persistent > grade 2 toxicity from prior cancer therapy. Symptomatic uncontrolled brain or leptomeningeal metastases. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression may be considered if they have received definitive treatment for this and evidence of clinically stable disease for 28 days. Known hypersensitivity to the components of niraparib. Major surgery within 3 weeks of starting the study or patient has not recovered from any effects of any major surgery. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. History or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study treatment, or is not in the best interest of the patient to participate. Immunocompromised patients. Patients with known active hepatic disease (i.e. , Hepatitis B or C).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jung Yun Lee
Phone
82-2-2228-2237
Email
jungyunlee@yuhs.ac
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jung Yun Lee
Organizational Affiliation
Severance Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yonsei University College of Medicine
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jung Yun Lee
Phone
82-2-2228-2237
Email
jungyunlee@yuhs.ac

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
(Describe the IPD sharing plan, including what IPD are to be shared with other researchers.)
Citations:
PubMed Identifier
34910393
Citation
Park J, Lim MC, Lee JK, Jeong DH, Kim SI, Choi MC, Kim BG, Lee JY. A single-arm, phase II study of niraparib and bevacizumab maintenance therapy in platinum-sensitive, recurrent ovarian cancer patients previously treated with a PARP inhibitor: Korean Gynecologic Oncology Group (KGOG 3056)/NIRVANA-R trial. J Gynecol Oncol. 2022 Mar;33(2):e12. doi: 10.3802/jgo.2022.33.e12. Epub 2021 Dec 6.
Results Reference
derived

Learn more about this trial

Niraparib and Bevacizumab Maintenance Therapy in Platinum-sensitive Recurrent Ovarian Cancer Patients Previously Treated With a PARP Inhibitor

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