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Alternative Dosing Of Niraparib To Decrease Dose Interruption In First Line Maintenance Treatment For Ovarian Cancer

Primary Purpose

Ovarian Cancer, Stage III Ovarian Cancer, Stage IV Ovarian Cancer

Status
Not yet recruiting
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Niraparib
Sponsored by
Sunnybrook Health Sciences Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer

Eligibility Criteria

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

Inclusion Criteria Patients must be able to understand the study, agree to participate and provide written, informed consent Patients must be female and age >/= 18 years of age Newly diagnosed, histologically confirmed, high-grade serous and grade 3 endometrioid ovarian, primary peritoneal, or fallopian tube cancer undergoing frontline treatment Stage III and IV cancer according to International Federation of Gynecology and Obstetrics (FIGO) 2018 criteria and all patients undergoing neoadjuvant chemotherapy (NACT) Patients must meet the following front-line treatment requirements: i. Patients must have completed a minimum of 4 cycles of platinum-based chemotherapy (carboplatin, cisplatin, oxaliplatin). Primary or interval debulking therapy and intraperitoneal chemotherapy are allowed. ii. Patients must have a complete response or partial tumor response (no lesion >1cm) to platinum-based regimen iii. CA-125 must be either: CA-125 in normal range or CA-125 decreased by 90% during front-line treatment and stable for a minimum of 7 days (does not increase by more than 15%) iv. Study drug can start within 12 weeks of completing chemotherapy Patients must be post-menopausal with no menses for >1 year, or surgically sterilized, or willing to use adequate contraception to prevent pregnancy or abstain from intercourse and agrees not to donate eggs for the purpose of reproduction from study enrollment until 6 months following the last dose of treatment. i. Patients of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin [hcg]) within 3 days prior to receiving the first dose of study treatment. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 Patients must have adequate organ function at enrollment, as follows: i. Absolute neutrophil count >/= 1.5 x109/L ii. Platelets >/= 100 x109/L iii. Hemoglobin >/= 100 g/L without transfusion iv. Creatinine clearance >/= 60 mL/min using the Cockcroft-Gault equation v. Total bilirubin </= 1.5 times the upper limit of normal (ULN) or direct bilirubin < 1 times the upper limit of normal vi. Aspartate aminotransferase and Alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN Patients with hypertension should have their blood pressure adequately treated and controlled prior to starting study treatment Patients must be able to take oral medications Patients must agree to complete blood samples prior to cycle 1, then weekly for the first month and as outlined in the protocol Exclusion Criteria: Patient's age is <18 years. Patient who are pregnant, breastfeeding, or expecting to conceive children during the study treatment of for 6 months after completion of the study treatment. Patients with a known hypersensitivity to niraparib or any of its components Patients who have received a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor as part of their previous treatment or participated in a trial where PARP inhibitors were administered in one arm of the trial. Patients enrolled in another investigational trial Patients who received another investigational therapy within 4 weeks or 5 halflives of the investigational agent, whichever is longer Patients with previous persistent (>4 weeks) or >/= grade 3 hematologic toxicity or fatigue from prior cancer therapy. Patients with known history of myelodysplastic syndrome or pre-treatment cytogenetic testing at risk for myelodysplastic syndrome or acute myeloid leukemia Patients receiving concurrent, prohibited medications Patients with previous major surgery within 3 weeks of starting study treatment and must have recovered from any effects of previous surgery. Patients with ascites drained within 4 weeks of starting study treatment Patients receiving palliative radiotherapy to >20% of bone marrow within 2 weeks or any other radiotherapy within 1 week of study treatment Patients receiving a transfusion (platelets or red blood cells) within 4 weeks of treatment Patients planning to donate blood during the study or 90 days after treatment. Patients with a diagnosis of another invasive cancer (other than ovarian cancer), within 2 years prior to randomization (except basal or squamous cell carcinoma of the skin that has been definitively treated i. Patients with uncontrolled brain or leptomeningeal metastases. Controlled brain or leptomeningeal metastasis is defined as: ii. Central nervous system disease that has undergone treatment with radiation or chemotherapy > 1 month before study entry No new or progressive signs or symptoms, stable steroid dose x 4 weeks or not taking steroids Patients considered poor medical risk due to serious, uncontrolled medical disorder, non-malignant systemic disease, or active uncontrolled infection i. Patients with known HIV considered high risk for serious and fatal outcome Patients with evidence of any condition, therapy, or laboratory abnormality that might confound study results or patient participation for full duration of study (Ex. Myelodysplastic syndrome, anemia, leukopenia, neutropenia, thrombocytopenia, etc) Patients who are immunocompromised (Patients with splenectomy are allowed) Patients with known, active hepatic disease (Ex. Hepatitis B or C), active biliary disease (exceptions for Gilbert's syndrome, asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease as per investigator assessment) Patients with QT prolongation >470 milliseconds at screening Patients with a known breast cancer susceptibility gene (BRCA1 and 2) mutation (as they routinely receive olaparib at our institution) If BRCA unknown they are not excluded. Patients with a history of posterior reversible encephalopathy syndrome (PRES) Patients who have had a live vaccine within 30 days of planned start date of study treatment Patients with gastrointestinal abnormalities that may limit absorption Patients with significant cardiovascular disease Patients undergoing serial blood counts to achieve a value to meet eligibility Patients receiving blood product transfusions in order to meet eligibility criteria

Sites / Locations

  • Sunnybrook Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single arm- Niraparib

Arm Description

Oral niraparib will be administered in a dose escalation design where patients will start at a dose of 100 mg PO daily for the first two cycles, then 200 mg PO daily for the third and fourth cycle. Patients will remain on the individualized dose until either they experience an adverse event and require a dose reduction or they have disease progression.

Outcomes

Primary Outcome Measures

Incidence of thrombocytopenia
Incidence of thrombocytopenia <100 x 109/L requiring a treatment interruption

Secondary Outcome Measures

Incidence of dose reduction due to thrombocytopenia
Incidence of discontinuation due to thrombocytopenia
Incidence of other hematologic toxicity
Incidence of dose reduction due to other hematologic toxicity
Incidence of discontinuation due to other hematologic toxicity
Incidence of other toxicities
Incidence of dose reduction due to other toxicities
Incidence of discontinuation due to other toxicities
Incidence of discontinuation due to disease progression
Incidence of discontinuation for other reasons
Progression-free survival at 24 months

Full Information

First Posted
July 18, 2023
Last Updated
August 8, 2023
Sponsor
Sunnybrook Health Sciences Centre
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT05961124
Brief Title
Alternative Dosing Of Niraparib To Decrease Dose Interruption In First Line Maintenance Treatment For Ovarian Cancer
Official Title
A Phase II, Single-Arm Trial Assessing Alternative Dosing Of Niraparib To Decrease Dose Interruption In First Line Maintenance Treatment For Ovarian Cancer: Dose Escalation
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
September 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sunnybrook Health Sciences Centre
Collaborators
GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this clinical trial is to test alternative dosing of niraparib in patients with newly diagnosed high-grade, advanced stage ovarian cancer. The main questions it aims to answer are: What is the incidence of hematologic and other adverse events? What is the incidence of dose interruption, dose reduction and discontinuation? What is the length of time of progression-free survival at 24 months?
Detailed Description
This is a single arm phase II study in patients with newly diagnosed high-grade, advanced stage ovarian cancer. Patients must have received a minimum of 4 cycles of front-line platinum-based chemotherapy with a complete response or partial response (no measurable lesion >1 cm and normal cancer antigen (CA -25) after completion of chemotherapy) and primary or interval debulking surgery. This study aims to evaluate the incidence of hematologic and other adverse events and the incidence of dose interruption, dose reduction and discontinuation, and progression-free survival at 24 months with a niraparib dose escalation design. Study enrollment is planned to include 40 patients at one site.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Stage III Ovarian Cancer, Stage IV Ovarian Cancer, High Grade Ovarian Serous Adenocarcinoma

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Single arm- Niraparib
Arm Type
Experimental
Arm Description
Oral niraparib will be administered in a dose escalation design where patients will start at a dose of 100 mg PO daily for the first two cycles, then 200 mg PO daily for the third and fourth cycle. Patients will remain on the individualized dose until either they experience an adverse event and require a dose reduction or they have disease progression.
Intervention Type
Drug
Intervention Name(s)
Niraparib
Other Intervention Name(s)
Zejula
Intervention Description
Niraparib (Zejula) will be administered as an oral treatment once daily (continuously in a 28-day cycle). Niraparib will be administered in a dose escalation design where patients will start at a dose of 100 mg PO daily for the first two cycles (28-days each cycle), if tolerated, the dose will be increased to 200 mg PO daily for the third and fourth cycle.
Primary Outcome Measure Information:
Title
Incidence of thrombocytopenia
Description
Incidence of thrombocytopenia <100 x 109/L requiring a treatment interruption
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Incidence of dose reduction due to thrombocytopenia
Time Frame
2 years
Title
Incidence of discontinuation due to thrombocytopenia
Time Frame
2 years
Title
Incidence of other hematologic toxicity
Time Frame
2 years
Title
Incidence of dose reduction due to other hematologic toxicity
Time Frame
2 years
Title
Incidence of discontinuation due to other hematologic toxicity
Time Frame
2 years
Title
Incidence of other toxicities
Time Frame
2 years
Title
Incidence of dose reduction due to other toxicities
Time Frame
2 years
Title
Incidence of discontinuation due to other toxicities
Time Frame
2 years
Title
Incidence of discontinuation due to disease progression
Time Frame
2 years
Title
Incidence of discontinuation for other reasons
Time Frame
2 years
Title
Progression-free survival at 24 months
Time Frame
2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Patients must be able to understand the study, agree to participate and provide written, informed consent Patients must be female and age >/= 18 years of age Newly diagnosed, histologically confirmed, high-grade serous and grade 3 endometrioid ovarian, primary peritoneal, or fallopian tube cancer undergoing frontline treatment Stage III and IV cancer according to International Federation of Gynecology and Obstetrics (FIGO) 2018 criteria and all patients undergoing neoadjuvant chemotherapy (NACT) Patients must meet the following front-line treatment requirements: i. Patients must have completed a minimum of 4 cycles of platinum-based chemotherapy (carboplatin, cisplatin, oxaliplatin). Primary or interval debulking therapy and intraperitoneal chemotherapy are allowed. ii. Patients must have a complete response or partial tumor response (no lesion >1cm) to platinum-based regimen iii. CA-125 must be either: CA-125 in normal range or CA-125 decreased by 90% during front-line treatment and stable for a minimum of 7 days (does not increase by more than 15%) iv. Study drug can start within 12 weeks of completing chemotherapy Patients must be post-menopausal with no menses for >1 year, or surgically sterilized, or willing to use adequate contraception to prevent pregnancy or abstain from intercourse and agrees not to donate eggs for the purpose of reproduction from study enrollment until 6 months following the last dose of treatment. i. Patients of childbearing potential must have a negative serum or urine pregnancy test (beta human chorionic gonadotropin [hcg]) within 3 days prior to receiving the first dose of study treatment. Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 Patients must have adequate organ function at enrollment, as follows: i. Absolute neutrophil count >/= 1.5 x109/L ii. Platelets >/= 100 x109/L iii. Hemoglobin >/= 100 g/L without transfusion iv. Creatinine clearance >/= 60 mL/min using the Cockcroft-Gault equation v. Total bilirubin </= 1.5 times the upper limit of normal (ULN) or direct bilirubin < 1 times the upper limit of normal vi. Aspartate aminotransferase and Alanine aminotransferase ≤ 2.5 x ULN unless liver metastases are present, in which case they must be ≤ 5 x ULN Patients with hypertension should have their blood pressure adequately treated and controlled prior to starting study treatment Patients must be able to take oral medications Patients must agree to complete blood samples prior to cycle 1, then weekly for the first month and as outlined in the protocol Exclusion Criteria: Patient's age is <18 years. Patient who are pregnant, breastfeeding, or expecting to conceive children during the study treatment of for 6 months after completion of the study treatment. Patients with a known hypersensitivity to niraparib or any of its components Patients who have received a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor as part of their previous treatment or participated in a trial where PARP inhibitors were administered in one arm of the trial. Patients enrolled in another investigational trial Patients who received another investigational therapy within 4 weeks or 5 halflives of the investigational agent, whichever is longer Patients with previous persistent (>4 weeks) or >/= grade 3 hematologic toxicity or fatigue from prior cancer therapy. Patients with known history of myelodysplastic syndrome or pre-treatment cytogenetic testing at risk for myelodysplastic syndrome or acute myeloid leukemia Patients receiving concurrent, prohibited medications Patients with previous major surgery within 3 weeks of starting study treatment and must have recovered from any effects of previous surgery. Patients with ascites drained within 4 weeks of starting study treatment Patients receiving palliative radiotherapy to >20% of bone marrow within 2 weeks or any other radiotherapy within 1 week of study treatment Patients receiving a transfusion (platelets or red blood cells) within 4 weeks of treatment Patients planning to donate blood during the study or 90 days after treatment. Patients with a diagnosis of another invasive cancer (other than ovarian cancer), within 2 years prior to randomization (except basal or squamous cell carcinoma of the skin that has been definitively treated i. Patients with uncontrolled brain or leptomeningeal metastases. Controlled brain or leptomeningeal metastasis is defined as: ii. Central nervous system disease that has undergone treatment with radiation or chemotherapy > 1 month before study entry No new or progressive signs or symptoms, stable steroid dose x 4 weeks or not taking steroids Patients considered poor medical risk due to serious, uncontrolled medical disorder, non-malignant systemic disease, or active uncontrolled infection i. Patients with known HIV considered high risk for serious and fatal outcome Patients with evidence of any condition, therapy, or laboratory abnormality that might confound study results or patient participation for full duration of study (Ex. Myelodysplastic syndrome, anemia, leukopenia, neutropenia, thrombocytopenia, etc) Patients who are immunocompromised (Patients with splenectomy are allowed) Patients with known, active hepatic disease (Ex. Hepatitis B or C), active biliary disease (exceptions for Gilbert's syndrome, asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease as per investigator assessment) Patients with QT prolongation >470 milliseconds at screening Patients with a known breast cancer susceptibility gene (BRCA1 and 2) mutation (as they routinely receive olaparib at our institution) If BRCA unknown they are not excluded. Patients with a history of posterior reversible encephalopathy syndrome (PRES) Patients who have had a live vaccine within 30 days of planned start date of study treatment Patients with gastrointestinal abnormalities that may limit absorption Patients with significant cardiovascular disease Patients undergoing serial blood counts to achieve a value to meet eligibility Patients receiving blood product transfusions in order to meet eligibility criteria
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dr. Allan Covens, MD
Phone
416-480-4026
Email
al.covens@sunnybrook.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dr. Allan Covens, MD
Organizational Affiliation
Sunnybrook Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sunnybrook Research Institute
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N3M5
Country
Canada
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nithla Mohanathas
Email
nithla.mohanathas@sunnybrook.ca
First Name & Middle Initial & Last Name & Degree
Dr. Allan Covens, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Alternative Dosing Of Niraparib To Decrease Dose Interruption In First Line Maintenance Treatment For Ovarian Cancer

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