NIRAPK : Study of the Relationship(s) Between Clinical, Biological and Pharmacokinetic Metrics and Toxicities When Niraparib is Used as Maintenance Treatment for Ovarian Cancer Patients. (NIRAPK)

April 19, 2022 updated by: Hospices Civils de Lyon

Study of the Relationship(s) Between Clinical, Biological and Pharmacokinetic Metrics and Toxicities When Niraparib is Used as Maintenance Treatment (300mg or 200 mg/Day) for Ovarian Cancer Patients.

Ovarian cancer is the seventh most common cancer in women worldwide and is the leading cause of gynecologic cancer deaths in high-income countries.

Standard treatment for newly diagnosed advanced ovarian cancer consist of cytoreductive surgery and platinum-based chemotherapy with or without concurrent and maintenance bevacizumab, a vascular endothelial growth factor (VEGF) inhibitor.

A majority of women with epithelial ovarian cancer respond well to first-line platinum-based chemotherapy. There is however a high rate of relapse/recurrence (disease progression ranging from 10 to 26 months).

Poly ADP ribose polymerase inhibitors (PARPi), a new class of therapeutic molecules have recently revolutionized this paradigm, demonstrating progression-free survival (PFS) advantages in several trials.

The PARPi molecule Niraparib has obtained its market authorization after the NOVA trial as second maintenance treatment line, irrespectively of patients' BRCA-mutated gene or HR status.

Since, results of the Phase III trial PRIMA, have demonstrated that Niraparib can also provided a significant PFS increase as first line maintenance treatment, for adult patients with platinum-sensitive, relapsed, high grade serous epithelial ovarian cancer who are in response (complete response or partial response) to platinum-based chemotherapy, irrespectively of their BRCA-mutated gene or HR status.

However, despite its high therapeutic potential, Niraparib at standard dose (200 or 300mg/day) is known to lead to hematologic toxicity and/or nephrotoxicity. This was demonstrated during the NOVA trial (the dose of Niraparib having to be reduced in 80% of the patients to reduce toxicity).

A retrospective study of the NOVA trial indicates that 2 predictive factors leading to hematologic toxicity were a weight <77kg and an initial platelet count <175 G/L. However, it seems more complex as 50% of patients with an initial weight between 58 and 77kg have not reported thrombocytopenia. Same for platelet count. Creatinine clearance below 60ml/min and an hypoalbuminemia <35 g/l have also been identified in another study as predictive factors to thrombocytopenia.

The inter-individual heterogeneity in terms of toxicity regarding Niraparib is high and still not well understood.

The aim of our study is therefore to better identify which clinical, biological and pharmacokinetic metrics can be considered as toxicity induction causes when Niraparib is used as maintenance treatment (200 or 300mg/day) for ovarian cancer patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

42

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Pierre-Bénite, France, 69495
        • Recruiting
        • Hôpital Lyon sud, Institut de Cancérologie des Hospices Civils de Lyon
        • Principal Investigator:
          • Benoit You
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Patient Study Information and written informed consent
  • Social Security Affiliation
  • Patient > 18 years old.
  • Ovarian, tubular or peritoneal high-grade epithelial carcinoma, histologically proven. Recommendation of a maintenance treatment with Niraparib at standard dose (200-300mg/day)
  • Glomerular filtration rate with standardized serum creatinine values using CKD-EPI formula ≥ 30ml/min/1.73m2 (https://www.kidney.org/professionals/kdoqi/gfr_calculator)
  • Normal liver function with bilirubin < 1.5N
  • 6-8 weeks break between last chemotherapy and Niraparib treatment initiation.
  • Patient with an effective birth control

Exclusion Criteria:

  • Minor patient
  • Patient not able to understand the aim of the study or under curatorship
  • Low grade carcinoma
  • Pregnant or breastfeeding patient
  • Hypersensivity to an active substance present in niraparib

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pharmacokinetics, Dosage of Niraparib
Patients received 3 cycles of Niraparib (200 mg or 300 mg/day). Each cycle lasts 28 days. Serum niraparib assays will be performed for all patients over 3 courses immediately prior to treatment (Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1). Close-up kinetic measurements will also be taken at 1 Hour, 2 Hours, 4 Hours, 6 Hours and 24 Hours at Cycle 1 Day 15.
Biological: Pharmacokinetics, Dosage of Niraparib
The biological samples collected during the NIRAPK study will be blood only. The complete biological work-up will be processed in the same way as the usual routine care procedure. Serum niraparib will be measured over 3 courses just prior to treatment (Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1). Close-up kinetic measurements will also be taken at 1 Hour, 2 Hours, 4 Hours, 6 Hours and 24 Hours at Cycle 1 Day 15.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of metrics (clinical, biological, pharmacokinetic) that are considered as toxicity induction causes (hematological toxicity or nephrotoxicity)
Time Frame: Month 10; after all the blood sample collection is achieved for all included patients.
Blood will be sampled at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1 and based on the obtained results, it will be seek if a link can be established between the clinical, biological and pharmacokinetic metrics and the observed toxicity.
Month 10; after all the blood sample collection is achieved for all included patients.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of the average pharmacokinetic metrics observed in our study panel patients.
Time Frame: Month 10; after all the blood sample collection is achieved for all included patients..
Blood will be sampled at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1 and based on the obtained results, the average metrics of pharmacokinetic parameters will be determined.
Month 10; after all the blood sample collection is achieved for all included patients..
Relationship between the pharmacokinetic metrics and the PFS at 24 months.
Time Frame: Month 34; after last patient inclusion (Month 10) + 24 months.
Blood will be sampled at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1 and based on the obtained results, it will be determined if a link can be established between the pharmacokinetic metrics and the PFS at 24 months
Month 34; after last patient inclusion (Month 10) + 24 months.
Relationship between the quality of life and the observed toxicity assessed by the "EORTC OVARIAN" questionnaire
Time Frame: Month 10, after last patient enrolment.
Analysis of quality of life by "QLQ OV28" questionnaire score collected at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1 and observed toxicity.
Month 10, after last patient enrolment.
Relationship between the quality of life and the observed toxicity assessed by the "Charlson Score" questionnaire
Time Frame: Month 10, after last patient enrolment.
Analysis of quality of life by "Charlson Score" questionnaire score collected at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1 and observed toxicity.
Month 10, after last patient enrolment.
Relationship between the quality of life and the observed toxicity assessed by the "Assessment of polymedication" questionnaire
Time Frame: Month 10, after last patient enrolment.
Analysis of quality of life by "Assessment of polymedication" questionnaire score collected at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1 and observed toxicity.
Month 10, after last patient enrolment.
Relationship between the quality of life and the observed toxicity assessed by the "Recording of food intake and monitoring of eating habits" questionnaire
Time Frame: Month 10, after last patient enrolment.
Analysis of quality of life by "Recording of food intake and monitoring of eating habits" questionnaire score collected at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and Cycle 3 Day 1 and observed toxicity.
Month 10, after last patient enrolment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 5, 2021

Primary Completion (Anticipated)

May 5, 2026

Study Completion (Anticipated)

May 5, 2026

Study Registration Dates

First Submitted

April 20, 2021

First Submitted That Met QC Criteria

April 22, 2021

First Posted (Actual)

April 27, 2021

Study Record Updates

Last Update Posted (Actual)

April 20, 2022

Last Update Submitted That Met QC Criteria

April 19, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL20_0989

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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.

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