NIRAPK: Study of the relationships between pharmacokinetic properties (PK) and hematological toxicity of niraparib in ovarian cancer

2024-513856-14-00 Protocol 69HCL20_0989 Therapeutic use (Phase IV) Ended

Start 5 May 2021 · End 17 Apr 2025 · Status Ended · 1 EU/EEA countries · 3 sites · Protocol 69HCL20_0989

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ended
Participants planned 42
Countries 1
Sites 3

Patients with high-grade serous epithelial ovarian, tubal or primary peritoneal cancers

Determination of the existence of links between patient-specific clinical/biological/therapeutic covariates and/or pharmacokinetic parameters of niraparib on the occurrence of hematological and/or renal toxicity(s) when used within the framework of its Marketing Authorization or ATU at 300 mg/day or at 200 mg/day in a …

Key facts

Sponsor
Hospices Civils De Lyon
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Female
Therapeutic area
Diseases [C] - Female Urogenital Diseases and Pregnancy Complications [C13]
Trial duration
5 May 2021 → 17 Apr 2025
Decision date (initial)
2024-07-10
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No

External identifiers

EU CT number
2024-513856-14-00
EudraCT number
2020-005918-17
ClinicalTrials.gov
NCT04861181

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic

Determination of the existence of links between patient-specific clinical/biological/therapeutic covariates and/or pharmacokinetic parameters of niraparib on the occurrence of hematological and/or renal toxicity(s) when used within the framework of its Marketing Authorization or ATU at 300 mg/day or at 200 mg/day in a reduced dose commonly prescribed, as maintenance treatment for high-grade serous ovarian cancer BRCA mutated or not.

Secondary objectives 4

  1. Determination of clinical/biological/therapeutic and dietary covariates influencing the pharmacokinetic parameters of niraparib
  2. Determination of the existence of a link between pharmacokinetic parameters and effectiveness of niraparib
  3. Development of a prognostic algorithm for individual adjustment of niraparib doses with a view to optimizing the benefit/risk ratio.
  4. Assessment of the impact of toxicities on quality of life (QLQ-OV28 scale)

Conditions and MedDRA coding

Patients with high-grade serous epithelial ovarian, tubal or primary peritoneal cancers

VersionLevelCodeTermSystem organ class
20.0 PT 10061328 Ovarian epithelial cancer 100000004864

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Niraparib
Prospective, single-center, multi-site study
Not Applicable None Niraparib: 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.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

  1. Women aged over 18
  2. Histologically proven high grade serous epithelial ovarian, tubal or primary peritoneal cancer
  3. Patient who has already received 4 to 6 courses of platinum-based chemotherapy and for whom there is an indication for maintenance treatment with niraparib at a standard dose of 300 mg/day, or at a reduced dose of 200 mg/day at investigator's choice
  4. Initial glomerular filtration rate according to CKD-EPI formula adjusted for cystatin C ≥ 30ml/min/1.73m2 ((https://www.kidney.org/professionals/kdoqi/gfr_calculator)
  5. Normal liver function with bilirubinemia < 1.5N
  6. Interval of 6 to 8 weeks between the last course of platinum-based chemotherapy and the start of treatment with niraparib
  7. For women of childbearing age: contraception deemed effective during treatment and up to 6 months after stopping treatment (hormonal contraception inhibiting ovulation (estrogen + progesterone or progesterone alone), IUD, tubal ligation, abstinence sexual, vasectomy spouse).
  8. Patient having been informed and having given signed informed consent
  9. Patient affiliated to a social security scheme or beneficiary of such a scheme

Exclusion criteria 5

  1. Minor patients
  2. Pregnant or breastfeeding patients
  3. Patients unable to understand the protocol, or under guardianship-curatorship
  4. Low grade carcinoma
  5. Hypersensitivity to the active substance of niraparib or one of these excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Identification of clinical/biological/pharmacokinetic/therapeutic factors leading to hematological and/or renal toxicology(s).

Secondary endpoints 4

  1. Relation of the average pharmacokinetic parameters observed in patients according to the clinical/biological/therapeutic and dietary parameters studied.
  2. Relationship between the pharmacokinetic parameters measured and the PFS at 24 months.
  3. Creation of predictive models using logistic models or PK-PD models with direct or indirect effects.
  4. Measurement of quality of life and correlation with observed toxicities.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Zejula 100 mg hard capsules

PRD5625301 · Product

Active substance
Niraparib Tosilate Monohydrate
Pharmaceutical form
CAPSULE, HARD
Route of administration
ORAL USE
Max daily dose
300 mg milligram(s)
Max total dose
23100 mg milligram(s)
Max treatment duration
77 Day(s)
Authorisation status
Authorised
ATC code
L01XK02 — -
Marketing authorisation
EU/1/17/1235/001
MA holder
GLAXOSMITHKLINE (IRELAND) LIMITED
MA country
EU
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospices Civils De Lyon

Sponsor organisation
Hospices Civils De Lyon
Address
3 Quai Des Celestins, Bp 2251 Bp 2251
City
Lyon Cedex 02
Postcode
69229
Country
France

Scientific contact point

Organisation
Hospices Civils De Lyon
Contact name
Pr YOU

Public contact point

Organisation
Hospices Civils De Lyon
Contact name
Pr YOU

Locations

1 EU/EEA country · 3 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ended 42 3
Rest of world 0

Investigational sites

France

3 sites · Ended
Hospices Civils De Lyon
Service d'oncologie médicale, 165 Chemin Du Grand Revoyet, 69310, Pierre Benite
Hospices Civils De Lyon
Service d'oncologie médicale, 103 Grande Rue De La Croix Rousse, 69317, Lyon Cedex 04
Hospices Civils De Lyon
Service d'oncologie méciale, 59 Boulevard Pinel, 69500, Bron

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2021-05-05 2025-04-17 2021-05-05 2023-05-24

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-06-11 France Acceptable
2024-07-10
2024-07-10