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

NCT05961124 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 5397
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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?

Conditions

Ovarian Cancer; Stage III Ovarian Cancer; Stage IV Ovarian Cancer; High Grade Ovarian Serous Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Incidence of thrombocytopenia

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

  2 years

Secondary Outcomes (11)

• Incidence of dose reduction due to thrombocytopenia

  2 years

• Incidence of discontinuation due to thrombocytopenia

  2 years

• Incidence of other hematologic toxicity

  2 years

• Incidence of dose reduction due to other hematologic toxicity

  2 years

• Incidence of discontinuation due to other hematologic toxicity

  2 years

Study Arms (1)

Single arm- Niraparib

EXPERIMENTAL

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.

Drug: Niraparib

Interventions

Niraparib DRUG

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.

Also known as: Zejula

Single arm- Niraparib

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Sunnybrook Research Institute

Toronto, Ontario, M4N3M5, Canada

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

niraparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Study Officials

• Dr. Allan Covens, MD

  Sunnybrook Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr. Allan Covens, MD

CONTACT

416-480-4026; al.covens@sunnybrook.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2023
• First Posted: July 27, 2023
• Study Start: August 21, 2023
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2027
• Last Updated: November 22, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)