Homologous Recombination DeficiencyPhase 2NCT05461690
Phase II Study of Niraparib in Metastatic TNBC Patients With Homologous Recombination Deficiency
A Phase 2 study testing Niraparib in people with Homologous Recombination Deficiency and Triple Negative Breast Cancer, run by Zhejiang Cancer Hospital.
Trial summary
The incidence of homologous recombination deficiency in metastatic triple negative breast cancer was 52%-59%，PARP plays a key role in sensing DNA damage and converting it into intracellular signals that activate the base excision repair (BER) and single-strand break repair pathways. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Homologous Recombination Deficiency, Triple Negative Breast Cancer
- What is being tested?
- Niraparib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2022to 30 Jun 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient is female at least 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Life expectancy longer than 6 months.
- Patients with histologically confirmed metastatic breast cancer must have disease that is HER2-negative, estrogen receptor-negative, and progesterone receptor-negative (ie, TNBC).
- Patient has measurable lesions by RECIST v1.1.
- Patients has archival tumor tissue available or a fresh biopsy must be obtained prior to study treatment initiation for HRD test. The HRD test results must be positive (HRR mutation or/and HRD score≥42).
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- Patients had received no more than two previous chemotherapy regimens for metastatic disease, and they had received neoadjuvant or adjuvant treatment or treatment for metastatic disease with an anthracycline (unless it was contraindicated) or a taxane.
- Previous neoadjuvant or adjuvant treatment with platinum or/and anthracycline were allowed if at least 6 months had elapsed since the last dose. Previous treatment with platinum or/and anthracycline for metastatic disease were allowed if there was no evidence that disease progression had occurred during treatment.
- Patient has adequate organ function, defined as:
- Absolute neutrophil count (ANC) ≥ 1,500/μL(growth factor support treatment shall not be used within 7 days after the start of study treatment）
- Platelets ≥ 100,000/μL(platelet transfusion or any form of platelet raising therapy shall not be used within 2 weeks after the start of the study)
- Hemoglobin ≥ 9 g/dL(blood transfusion shall not be used within 2 weeks after the start of study treatment. EPO support treatment shall not be used within 7 days after the start of study treatment.)
- Serum creatinine ≤ 1.5× upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min using Cockcroft-Gault equation for patients with creatinine levels > 1.5× institutional ULN
- Total bilirubin ≤ 1.5× ULN OR direct bilirubin ≤ 1× ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5× ULN unless liver metastases are present, in which case they must be ≤ 5× ULN
- Urine protein ≤ (+), or 24-hour urine protein quantity is less than 1g
- International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) ≤ 1.5× ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Female patient has a negative serum pregnancy test within 7days prior to taking study medication if of childbearing potential, or agrees to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment, or be of non-childbearing potential. Non-childbearing potential is defined as (by other than medical reasons).
- Female patients must agree not to breastfeed during the study period or within 180 days after the last dose of study treatment.
- Patient agrees to blood samples during screening and at the end of treatment for cytogenetic analysis.
Who cannot join
- Patients have received PARP inhibitors for metastatic breast cancer.
- Patients who are concurrently participating in any interventional clinical trial and have received an investigational therapy ≤ 4 weeks prior to initiation of protocol therapy or within at least 5 elimination half-lives of the investigational drug.
- Patients who have received radiotherapy with > 20% bone marrow coverage before treatment initiation, except for minor palliative radiotherapy within 1 weeks prior to enrollment.
- Patients with visceral crisis requiring chemotherapy.
- Patients with hypersensitivity to nilaparib.
- Patients receiving blood transfusions (platelets or red blood cells) ≤ 4 weeks prior to starting protocol therapy.
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- Patients who have received colony-stimulating factors (eg, granulocyte-colony stimulating factor [g-CSF], granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) 4 weeks prior to starting protocol therapy.
- Known history of platelet transfusions for chemotherapy-induced thrombocytopenia or ≥ Grade 3 hematologic toxicity from prior cancer therapy (lasting > 4 weeks and associated with most recent therapy).
- Patient has any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
- Patient has a serious, uncontrolled medical condition, non-malignant systemic disease, or active, uncontrolled infection.
- Patient has other types of cancer ≤ 2 years prior to starting protocol therapy.
- Patients with symptomatic brain metastasis or leptomeningeal metastasis.
- Patients with prior allogeneic bone marrow transplant or cord blood transplant.
- Patients who cannot swallow oral medication.
- Patients with gastrointestinal disorders that could interfere with absorption of the study drug.
- Patient has a systemic active autoimmune disease (use of disease modifying agents, corticosteroids, or immunosuppressive agents, etc.) within the past 2 years.
- Patients with a history of human immunodeficiency virus, active hepatitis B or C.
- Female patients who are pregnant or lactating or adults of childbearing potential not using effective contraceptive methods.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Phase II Study of Niraparib Single Agent in Metastatic Triple Negative Breast Cancer Patients With Homologous Recombination Deficiency
The incidence of homologous recombination deficiency in metastatic triple negative breast cancer was 52%-59%，PARP plays a key role in sensing DNA damage and converting it into intracellular signals that activate the base excision repair (BER) and single-strand break repair pathways. Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a subset of cancer cells with deficiencies in DNA repair pathways. This is a multicenter, single-arm, phase II study evaluating the efficacy and safety of niraparib in patients with HRD positive metastatic triple negative breast cancer.
Read the detailed description
Simon's two-stage optimization method is used to estimate the sample size. The first kind of error α Set to 0.1, type II error β Set to 0.25, P0 to 30%, P1 to 44%. 22 patients were enrolled in the first stage. If the number of effective cases ≤ 6, the trial was terminated. Otherwise, continue to enroll 26 patients in the second stage. If the number of effective cases in the two stages is ≤ 18, there is no need to further study the drug. Assuming an abscission rate of 5%, it is estimated that 50 subjects will be enrolled in the trial.
- Being tested
- Niraparib
- Keywords
- homologous recombination deficiency, Niraparib, triple negative breast cancer
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NiraparibDrug
Also called Zejula
200mg once a day for patients with body weight <77kg or baseline platelet count <150,000/µL, and 300mg once a day for patients with body weight ≥ 77kg and baseline platelet count ≥ 150,000/µL until disease progression or intolerable toxicity whichever occurs first.
| Study group | Role | What they receive |
|---|---|---|
| Niraparib group | Experimental | 200mg once a day for patients with body weight <77kg or baseline platelet count <150,000/µL, and 300mg once a day for patients with body weight ≥ 77kg and baseline platelet count ≥ 150,000/µL until disease progression or intolerable toxicity whichever occurs first. Receives: Drug: Niraparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
ORR is defined as the percentage of patients who achieved a best overall response of Complete Response (CR) or Partial Response (PR), per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions as assessed by the Investigator: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
Secondary outcomes (4)
Progression-Free Survival (PFS)
From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
Measured: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
Clinical Benefit Rate (CBR)
Percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD) lasting 24 weeks or longer as defined in RECIST v1.1.
Measured: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
Time to response (TTR)
TTR defined as the time from the date of the first dose of study treatment to the first objective tumor response when CR or PR is observed.
Measured: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
Overall survival (OS)
Time to death from any cause from the date of first dose of study treatment
Measured: From date of first dose until the date of death from any cause, assessed up to 60 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2022
- Study start1 Sep 2022 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion30 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Homologous Recombination DeficiencyStudies of the same condition, open and under way.
- More trials run by Zhejiang Cancer HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhejiang Cancer Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Sun Yat-sen University, Hunan Cancer Hospital, Fujian Cancer Hospital, Zhejiang University, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
- Responsible party
- Principal investigator, Wang Xiaojia, Zhejiang Cancer Hospital
- Investigators
- Xiaojia Wang, MD, Principal investigator, Zhejiang Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05461690
- Sponsor's protocol ID
- IRB-2022-329
- Status last verified
- Jul 2022
- First submitted
- 27 Jun 2022
- Last updated
- 18 Jul 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Niraparib Single Agent in Metastatic Triple Negative Breast Cancer Patients With Homologous Recombination Deficiency
- ClinicalTrials.gov ID
- NCT05461690
- Acronym / sponsor ID
- IRB-2022-329
- Keywords
- homologous recombination deficiency, Niraparib, triple negative breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Zhejiang Cancer HospitalUniversity, hospital or other
- Collaborators
- Sun Yat-sen University, Hunan Cancer Hospital, Fujian Cancer Hospital, Zhejiang University, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University
- Study start
- 1 Sep 2022 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 30 Jun 2025 (estimated)
- First posted
- 18 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The incidence of homologous recombination deficiency in metastatic triple negative breast cancer was 52%-59%，PARP plays a key role in sensing DNA damage and converting it into intracellular signals that activate the base excision repair (BER) and single-strand break repair pathways. Treatment with PARP inhibitors could represent a novel opportunity to selectively kill a subset of cancer cells with deficiencies in DNA repair pathways. This is a multicenter, single-arm, phase II study evaluating the efficacy and safety of niraparib in patients with HRD positive metastatic triple negative breast cancer.
Detailed description
Simon's two-stage optimization method is used to estimate the sample size. The first kind of error α Set to 0.1, type II error β Set to 0.25, P0 to 30%, P1 to 44%. 22 patients were enrolled in the first stage. If the number of effective cases ≤ 6, the trial was terminated. Otherwise, continue to enroll 26 patients in the second stage. If the number of effective cases in the two stages is ≤ 18, there is no need to further study the drug. Assuming an abscission rate of 5%, it is estimated that 50 subjects will be enrolled in the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Niraparib group | Experimental | Drug: Niraparib200mg once a day for patients with body weight <77kg or baseline platelet count <150,000/µL, and 300mg once a day for patients with body weight ≥ 77kg and baseline platelet count ≥ 150,000/µL until disease progression or intolerable toxicity whichever occurs first. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patient is female at least 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Life expectancy longer than 6 months.
- Patients with histologically confirmed metastatic breast cancer must have disease that is HER2-negative, estrogen receptor-negative, and progesterone receptor-negative (ie, TNBC).
- Patient has measurable lesions by RECIST v1.1.
Key exclusion criteria (18 listed)
- Patients have received PARP inhibitors for metastatic breast cancer.
- Patients who are concurrently participating in any interventional clinical trial and have received an investigational therapy ≤ 4 weeks prior to initiation of protocol therapy or within at least 5 elimination half-lives of the investigational drug.
- Patients who have received radiotherapy with > 20% bone marrow coverage before treatment initiation, except for minor palliative radiotherapy within 1 weeks prior to enrollment.
- Patients with visceral crisis requiring chemotherapy.
- Patients with hypersensitivity to nilaparib.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NiraparibAlso: Zejula200mg once a day for patients with body weight <77kg or baseline platelet count <150,000/µL, and 300mg once a day for patients with body weight ≥ 77kg and baseline platelet count ≥ 150,000/µL until disease progression or intolerable toxicity whichever occurs first. | Drug | Niraparib group |
Primary outcome
Objective Response Rate (ORR)
Time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
ORR is defined as the percentage of patients who achieved a best overall response of Complete Response (CR) or Partial Response (PR), per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions as assessed by the Investigator: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
4 secondary outcomes
Progression-Free Survival (PFS)
Time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
Clinical Benefit Rate (CBR)
Time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
Time to response (TTR)
Time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.
Overall survival (OS)
Time frame: From date of first dose until the date of death from any cause, assessed up to 60 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaojia Wang, MD principal investigator
Zhejiang Cancer Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Niraparib in people with Homologous Recombination Deficiency and Triple Negative Breast Cancer, run by Zhejiang Cancer Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 18 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaojia Wang, MD (13906500190, wxiaojia0803@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2022.