- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05961124
Alternative Dosing Of Niraparib To Decrease Dose Interruption In First Line Maintenance Treatment For Ovarian Cancer
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
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?
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Dr. Allan Covens, MD
- Phone Number: 416-480-4026
- Email: al.covens@sunnybrook.ca
Study Locations
-
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Ontario
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Toronto, Ontario, Canada, M4N3M5
- Recruiting
- Sunnybrook Research Institute
-
Contact:
- Nithla Mohanathas
- Email: nithla.mohanathas@sunnybrook.ca
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Principal Investigator:
- Dr. Allan Covens, MD
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single arm- Niraparib
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.
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of thrombocytopenia
Time Frame: 2 years
|
Incidence of thrombocytopenia <100 x 109/L requiring a treatment interruption
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of dose reduction due to thrombocytopenia
Time Frame: 2 years
|
2 years
|
Incidence of discontinuation due to thrombocytopenia
Time Frame: 2 years
|
2 years
|
Incidence of other hematologic toxicity
Time Frame: 2 years
|
2 years
|
Incidence of dose reduction due to other hematologic toxicity
Time Frame: 2 years
|
2 years
|
Incidence of discontinuation due to other hematologic toxicity
Time Frame: 2 years
|
2 years
|
Incidence of other toxicities
Time Frame: 2 years
|
2 years
|
Incidence of dose reduction due to other toxicities
Time Frame: 2 years
|
2 years
|
Incidence of discontinuation due to other toxicities
Time Frame: 2 years
|
2 years
|
Incidence of discontinuation due to disease progression
Time Frame: 2 years
|
2 years
|
Incidence of discontinuation for other reasons
Time Frame: 2 years
|
2 years
|
Progression-free survival at 24 months
Time Frame: 2 years
|
2 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Dr. Allan Covens, MD, Sunnybrook Research Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Cystadenocarcinoma
- Neoplasms, Cystic, Mucinous, and Serous
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Ovarian Neoplasms
- Carcinoma, Ovarian Epithelial
- Cystadenocarcinoma, Serous
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Poly(ADP-ribose) Polymerase Inhibitors
- Niraparib
Other Study ID Numbers
- 5397
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Ovarian Cancer
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Roswell Park Cancer InstituteCompletedFallopian Tube Carcinoma | Primary Peritoneal Carcinoma | Stage IIA Ovarian Cancer | Stage IIB Ovarian Cancer | Stage IIC Ovarian Cancer | Stage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian Cancer | Stage IA Ovarian Cancer | Stage IB Ovarian Cancer | Stage IC... and other conditionsUnited States
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City of Hope Medical CenterNational Cancer Institute (NCI)CompletedCancer Survivor | Stage IIIA Ovarian Epithelial Cancer | Stage IIIB Ovarian Epithelial Cancer | Stage IIIC Ovarian Epithelial Cancer | Stage IIA Ovarian Epithelial Cancer | Stage IIB Ovarian Epithelial Cancer | Stage IIC Ovarian Epithelial Cancer | Stage IA Ovarian Epithelial Cancer | Stage IB Ovarian... and other conditionsUnited States
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Massachusetts General HospitalJohns Hopkins University; M.D. Anderson Cancer Center; National Cancer Institute... and other collaboratorsRecruitingOvarian Neoplasms | Fallopian Tube Neoplasms | Stage III Ovarian Cancer AJCC v8 | Stage IIIA Ovarian Cancer AJCC v8 | Stage IIIA1 Ovarian Cancer AJCC v8 | Stage IIIA2 Ovarian Cancer AJCC v8 | Stage IIIB Ovarian Cancer AJCC v8 | Stage IIIC Ovarian Cancer AJCC v8 | Stage IV Ovarian Cancer AJCC v8 | Stage... and other conditionsUnited States
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Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedOvarian Clear Cell Cystadenocarcinoma | Ovarian Endometrioid Adenocarcinoma | Ovarian Seromucinous Carcinoma | Ovarian Serous Cystadenocarcinoma | Stage IV Ovarian Germ Cell Tumor | Ovarian Sarcoma | Malignant Ovarian Epithelial Tumor | Ovarian Carcinosarcoma | Ovarian Brenner Tumor | Ovarian Mucinous... and other conditionsUnited States
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Gynecologic Oncology GroupNational Cancer Institute (NCI)CompletedStage IIA Fallopian Tube Cancer | Stage IIA Ovarian Cancer | Stage IIB Fallopian Tube Cancer | Stage IIB Ovarian Cancer | Stage IIC Fallopian Tube Cancer | Stage IIC Ovarian Cancer | Stage IIIA Fallopian Tube Cancer | Stage IIIA Ovarian Cancer | Stage IIIA Primary Peritoneal Cancer | Stage IIIB Fallopian... and other conditionsUnited States
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University of WashingtonNational Cancer Institute (NCI)CompletedCaregiver | Stage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
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Sidney Kimmel Cancer Center at Thomas Jefferson...CompletedStage I Breast Cancer | Stage I Uterine Corpus Cancer | Stage II Uterine Corpus Cancer | Stage III Uterine Corpus Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Stage IIIB Breast Cancer | Stage IA Breast Cancer | Stage IB Breast Cancer | Stage IIA Breast Cancer | Stage IIB Breast Cancer | Stage... and other conditionsUnited States
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Eve RodlerNot yet recruitingBreast Cancer | Ovarian Cancer | Breast Neoplasm | Breast Carcinoma | Breast Cancer Stage IV | Breast Cancer Stage I | Breast Cancer Stage II | Invasive Breast Cancer | Cancer, Breast | Breast Cancer Stage III | Ovary Cancer | Malignant Tumor of Breast | Ovarian Cancer Stage IIIC | Ovarian Cancer Stage IV | Ovarian Cancer... and other conditionsUnited States
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Gynecologic Oncology GroupNational Cancer Institute (NCI)RecruitingStage IIIA Ovarian Cancer | Stage IIIB Ovarian Cancer | Stage IIIC Ovarian Cancer | Stage IV Ovarian CancerUnited States
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University of WashingtonMinnesota Ovarian Cancer AllianceTerminatedStage III Ovarian Cancer AJCC v8 | Stage IIIA Ovarian Cancer AJCC v8 | Stage IIIA1 Ovarian Cancer AJCC v8 | Stage IIIA2 Ovarian Cancer AJCC v8 | Stage IIIB Ovarian Cancer AJCC v8 | Stage IIIC Ovarian Cancer AJCC v8 | Stage IV Ovarian Cancer AJCC v8 | Stage IVA Ovarian Cancer AJCC v8 | Stage IVB Ovarian... and other conditionsUnited States
Clinical Trials on Niraparib
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Tesaro, Inc.Completed
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Fudan UniversityRecruitingTreatment EfficacyChina
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Chongqing University Cancer HospitalRecruiting
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German Breast GroupGlaxoSmithKline; Stemline Therapeutics, Inc.Not yet recruitingBRCA1 Mutation | BRCA2 Mutation | PALB2 Gene Mutation | Hormone Receptor Positive HER-2 Negative Breast Cancer | Advanced or Metastatic Breast CancerGermany
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Sun Yat-sen UniversityRecruitingNasopharyngeal CarcinomaChina
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Abramson Cancer Center at Penn MedicineActive, not recruitingProstate AdenocarcinomaUnited States
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Hunan Cancer HospitalUnknown
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Institut Paoli-CalmettesGlaxoSmithKlineNot yet recruiting