Locally Advanced LeiomyosarcomaPhase 2NCT05174455
Niraparib for the Treatment of Leiomyosarcoma
A Phase 2 study testing Niraparib Tosylate Monohydrate in people with Locally Advanced Leiomyosarcoma and Metastatic Leiomyosarcoma, run by David Liebner, MD.
Trial summary
This phase II trial tests whether niraparib works to shrink tumor in patients with leiomyosarcoma. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Leiomyosarcoma, Metastatic Leiomyosarcoma, Stage III Retroperitoneal Sarcoma AJCC v8
- What is being tested?
- Niraparib Tosylate Monohydrate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2023to 31 Dec 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must have histologically documented LMS. Pathology review and confirmation of diagnosis will occur at the site enrolling the patient on this study.
- Patients must have had a recent, within six months of screening, tumor biopsy testing positive for pathogenic mutation or homozygous loss of either BARD1, BRCA1, BRCA2, BRIP1, PALB2, RAD51, RAD51B, RAD51C, or RAD51D using a clinically validated next-generation (NGS) sequencing panel.
- Variant pathogenicity will be arbitrated by the primary investigative team
- Patients must have locally advanced and unresectable or metastatic disease
- Patients must have disease which is measurable at study entry according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Additionally, patients must have a site of disease deemed accessible for biopsy at no or minimal risk to the patient (including through the use of image-guidance). If there are questions regarding the feasibility of biopsy, the case should be reviewed with interventional radiology or the appropriate department at the study site
- Patients must have had prior progression on, or intolerance to, at least one line of systemic therapy for advanced LMS. Adjuvant therapy administered after curative resection will not qualify as prior treatment. There is no upper limit on the number of prior therapies received
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- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- Participant must be >= 18 years of age
- Absolute neutrophil count >= 1,500/uL
- Platelets >= 100,000/uL
- Hemoglobin >= 9 g/dL
- Serum creatinine =< 1.5 x upper limit of normal (ULN) or calculated creatinine clearance >= 30 mL/min using the Cockcroft-Gault equation
- Total bilirubin =< 1.5 x ULN (=< 2.0 in patients with known Gilbert's syndrome) OR direct bilirubin =< 1 x ULN
- Aspartate aminotransferase and alanine aminotransferase =< 2.5 x ULN unless liver metastases are present, in which case they must be =< 5 x ULN
- Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy
- Female participant has either a negative highly sensitive urine or a serum pregnancy test within 72 hours prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 180 days after the last dose of study treatment, or is of nonchildbearing potential. Nonchildbearing potential is defined as follows (by other than medical reasons):
- >= 45 years of age and has not had menses for > 1 year
- Patients who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
- Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the patient must be willing to use 2 adequate barrier methods throughout the study, starting with the screening visit through 180 days after the last dose of study treatment. Information must be captured appropriately within the site's source documents. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient.
- Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the non-estrogen hormonal highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment
- Male participant agrees to use an adequate method of contraception starting with the first dose of study treatment through 90 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the established and preferred contraception for the patient
- Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent
- Participant must have normal blood pressure or adequately treated and controlled hypertension (i.e. systolic blood pressure =< 140 mmHg and diastolic blood pressure =< 90 mmHg).
Who cannot join
- Patients must not have had any previous treatment with any poly(adenosine diphosphate[ADP]-ribose) polymerase (PARP) inhibitors
- Participant must not be simultaneously enrolled in any interventional clinical trial
- Participant must not have had major surgery =< 4 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
- Participant must not have received investigational therapy =< 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy
- Participant receiving non-steroidal anti-estrogen agents must discontinue their use at least two weeks prior to study entry
- Participant has had radiation therapy encompassing > 20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy
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- Participant must not have a known hypersensitivity to niraparib components or excipients.
- Participant must not have received a transfusion (platelets or red blood cells) =<4 weeks prior to initiating protocol therapy
- Participant must not have received colony-stimulating factors (e.g., granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior to initiating protocol therapy
- Participant has had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy that persisted > 4 weeks and was related to the most recent treatment
- Participant must not have any known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
- Participant must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent
- Participant must not have had diagnosis, detection, or treatment of another type of cancer =< 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin and cervical cancer that has been definitively treated)
- Participant has leptomeningeal disease, carcinomatous meningitis, symptomatic brain metastases, or radiologic signs of central nervous system (CNS) hemorrhage.
- Note: Participants with asymptomatic brain metastases (i.e. off corticosteroids and anticonvulsants for at least 7 days) are permitted
- Participant has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [qualitative] is detected).
- Prior history of posterior reversible encephalopathy syndrome (PRES)
- History of severe renal impairment
- History of severe liver impairment
- Any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
About this study
Official title: Phase II Study of Niraparib for Leiomyosarcoma With Alterations in the Homologous Recombination DNA Repair Pathway
This phase II trial tests whether niraparib works to shrink tumor in patients with leiomyosarcoma. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate whether niraparib tosylate monohydrate (niraparib) shows preliminary evidence of clinical activity among subjects with leiomyosarcoma (LMS) with genomic alterations in the homologous recombination (HR) pathway as measured by the confirmed objective response rate (ORR).
SECONDARY OBJECTIVES:
- To evaluate the clinical benefit rate (CBR) associated with niraparib treatment in the study population.
II. To evaluate the progression free survival (PFS) associated with niraparib treatment in the study population.
III. To evaluate the overall survival (OS) associated with niraparib treatment in the study population.
IV. To evaluate the overall safety and tolerability of niraparib treatment in the study population.
EXPLORATORY OBJECTIVES:
- To evaluate predictive biomarkers of response to niraparib. II. To evaluate genomic mechanisms of resistance following treatment benefit with niraparib.
III. To evaluate previous treatment response as a marker of response to niraparib.
OUTLINE:
Patients receive niraparib orally (PO) once daily (QD). Cycles repeat every 28 days for 15 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 5 years or until death.
- Conditions
- Locally Advanced Leiomyosarcoma, Metastatic Leiomyosarcoma, Stage III Retroperitoneal Sarcoma AJCC v8, Stage IIIA Retroperitoneal Sarcoma AJCC v8, Stage IIIB Retroperitoneal Sarcoma AJCC v8, Stage IV Retroperitoneal Sarcoma AJCC v8
- Being tested
- Niraparib Tosylate Monohydrate
- Medical subject headings
- Leiomyosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Niraparib Tosylate MonohydrateDrug
Also called Zejula
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (Niraparib) | Experimental | Patients receive niraparib PO QD. Cycles repeat every 28 days for 15 months in the absence of disease progression or unacceptable toxicity. Receives: Drug: Niraparib Tosylate Monohydrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Confirmed objective response rate (ORR)
Defined as complete response + partial response measured by Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1). Will be calculated as the proportion of patients who achieve a response (complete response + partial response) within the first 6 months of treatment divided by the total number of evaluable patients. An evaluable patient is defined as an eligible patient who has received at least one dose of therapy. All evaluable patients will be included in calculating the ORR for the study along with corresponding 95% binomial confidence intervals (CIs) (assuming that the number of patients who respond is binomially distributed).
Measured: Within first 6 months of study treatment
Secondary outcomes (4)
Incidence of adverse events (AEs)
Frequency and severity of AEs and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. All patients who have received at least one dose of the therapeutic agents will be evaluable for toxicity and tolerability.
Measured: Up to 2 years after study treatment
Confirmed clinical benefit rate (CBR)
Defined as complete response + partial response + stable disease. Will be calculated with 95% binomial CIs.
Measured: Within first 6 months of study treatment
Progression-free survival (PFS)
Will initially be modeled using Kaplan-Meier methods, resulting in median survival times with 95% CI, assuming sufficient events have occurred.
Measured: From first treatment with the study drug to the earliest of either disease progression or death from any cause, assessed up to 2 years
Overall survival (OS)
Will initially be modeled using Kaplan-Meier methods, resulting in median survival times with 95% CI, assuming sufficient events have occurred.
Measured: From first treatment with the study drug to the death from any cause, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2021
- Study start1 Dec 2023 (estimated)
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
Why it stopped: PI decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced LeiomyosarcomaStudies of the same condition, open and under way.
- 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Liebner, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David Liebner, MD, Ohio State University Comprehensive Cancer Center
- Investigators
- David Liebner, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05174455
- Sponsor's protocol ID
- OSU-21214
- Other IDs
- NCI-2021-12582
- Status last verified
- Sep 2023
- First submitted
- 13 Dec 2021
- Last updated
- 18 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Niraparib for Leiomyosarcoma With Alterations in the Homologous Recombination DNA Repair Pathway
- ClinicalTrials.gov ID
- NCT05174455
- Acronym / sponsor ID
- OSU-21214
- Conditions
- Locally Advanced Leiomyosarcoma, Metastatic Leiomyosarcoma, Stage III Retroperitoneal Sarcoma AJCC v8, Stage IIIA Retroperitoneal Sarcoma AJCC v8, Stage IIIB Retroperitoneal Sarcoma AJCC v8, Stage IV Retroperitoneal Sarcoma AJCC v8
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI decision
- Enrolment
- 0 participants (actual)
- Lead sponsor
- David Liebner, MDUniversity, hospital or other
- Study start
- 1 Dec 2023 (estimated)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 30 Dec 2021 (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.
This phase II trial tests whether niraparib works to shrink tumor in patients with leiomyosarcoma. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate whether niraparib tosylate monohydrate (niraparib) shows preliminary evidence of clinical activity among subjects with leiomyosarcoma (LMS) with genomic alterations in the homologous recombination (HR) pathway as measured by the confirmed objective response rate (ORR).
SECONDARY OBJECTIVES:
- To evaluate the clinical benefit rate (CBR) associated with niraparib treatment in the study population.
II. To evaluate the progression free survival (PFS) associated with niraparib treatment in the study population.
III. To evaluate the overall survival (OS) associated with niraparib treatment in the study population.
IV. To evaluate the overall safety and tolerability of niraparib treatment in the study population.
EXPLORATORY OBJECTIVES:
- To evaluate predictive biomarkers of response to niraparib. II. To evaluate genomic mechanisms of resistance following treatment benefit with niraparib.
III. To evaluate previous treatment response as a marker of response to niraparib.
OUTLINE:
Patients receive niraparib orally (PO) once daily (QD). Cycles repeat every 28 days for 15 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 5 years or until death.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (Niraparib) | Experimental | Drug: Niraparib Tosylate MonohydratePatients receive niraparib PO QD. Cycles repeat every 28 days for 15 months in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Participant must have histologically documented LMS. Pathology review and confirmation of diagnosis will occur at the site enrolling the patient on this study.
- Patients must have had a recent, within six months of screening, tumor biopsy testing positive for pathogenic mutation or homozygous loss of either BARD1, BRCA1, BRCA2, BRIP1, PALB2, RAD51, RAD51B, RAD51C, or RAD51D using a clinically validated next-generation (NGS) sequencing panel.
- Patients must have locally advanced and unresectable or metastatic disease
- Patients must have disease which is measurable at study entry according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Additionally, patients must have a site of disease deemed accessible for biopsy at no or minimal risk to the patient (including through the use of image-guidance). If there are questions regarding the feasibility of biopsy, the case should be reviewed with interventional radiology or the appropriate department at the study site
- Patients must have had prior progression on, or intolerance to, at least one line of systemic therapy for advanced LMS. Adjuvant therapy administered after curative resection will not qualify as prior treatment. There is no upper limit on the number of prior therapies received
Key exclusion criteria (20 listed)
- Patients must not have had any previous treatment with any poly(adenosine diphosphate[ADP]-ribose) polymerase (PARP) inhibitors
- Participant must not be simultaneously enrolled in any interventional clinical trial
- Participant must not have had major surgery =< 4 weeks prior to initiating protocol therapy and participant must have recovered from any surgical effects
- Participant must not have received investigational therapy =< 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy
- Participant receiving non-steroidal anti-estrogen agents must discontinue their use at least two weeks prior to study entry
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 |
|---|---|---|
| Niraparib Tosylate MonohydrateAlso: ZejulaGiven PO | Drug | Treatment (Niraparib) |
Primary outcome
Confirmed objective response rate (ORR)
Time frame: Within first 6 months of study treatment
Defined as complete response + partial response measured by Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1). Will be calculated as the proportion of patients who achieve a response (complete response + partial response) within the first 6 months of treatment divided by the total number of evaluable patients. An evaluable patient is defined as an eligible patient who has received at least one dose of therapy. All evaluable patients will be included in calculating the ORR for the study along with corresponding 95% binomial confidence intervals (CIs) (assuming that the number of patients who respond is binomially distributed).
4 secondary outcomes
Incidence of adverse events (AEs)
Time frame: Up to 2 years after study treatment
Confirmed clinical benefit rate (CBR)
Time frame: Within first 6 months of study treatment
Progression-free survival (PFS)
Time frame: From first treatment with the study drug to the earliest of either disease progression or death from any cause, assessed up to 2 years
Overall survival (OS)
Time frame: From first treatment with the study drug to the death from any cause, assessed up to 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2023.
- The JameslineLink provided by the sponsor.
- 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.
David Liebner, MD principal investigator
Ohio State University Comprehensive Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Niraparib Tosylate Monohydrate in people with Locally Advanced Leiomyosarcoma and Metastatic Leiomyosarcoma, run by David Liebner, MD.
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 23 inclusion and 20 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: withdrawn, as of the sponsor's last update on 18 Sep 2023. 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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Confirmed objective response rate (ORR) (time frame: Within first 6 months of study treatment). 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 Sep 2023.