Etude : D0816C00025 / LYNPARZA



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Acronyme
Nom
Traitement
Type d'étude
MÀJ
Présentation de l'étude
Acronyme : D0816C00025

Nom : LYNPARZA

Traitement : Métastatique ou localement avancé

Type d'étude : Ciblage moléculaire / Innovation thérapeutique

Dernière MÀJ : 17/02/2020
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Étude de phase I, ouverte, en groupes parallèles, visant à évaluer la sécurité et la tolérance, l’efficacité et la pharmacocinétique de l'olaparib chez des patients pédiatriques présentant des tumeurs solides

Spécialité : Toutes tumeurs solides
Localisation : C - Toutes localisations
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : A Phase I open-label, multicentre study to determine the RP2D of olaparib monotherapy in the paediatric population, and to evaluate the safety, tolerability, PK, PDx and preliminary efficacy of olaparib monotherapy in paediatric patients from ≥6 months to <18 years of age at enrolment, with relapsed or refractory non-CNS solid tumours for whom there are no standard treatment options. It is anticipated that eligible patients fulfilling all of the inclusion criteria and none of the exclusion criteria, will include but will not be limited to those with osteosarcoma, rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, Ewing Sarcoma and neuroblastoma.


- Experimental: Cohort A: ≥12 to <18 years
Patients will receive a single dose of olaparib on Day 1, followed by initiation of bd continuous dosing from Day 2 onwards. Olaparib tablets should be taken at the same time each day (morning and evening), approximately 12 hours apart with one glass of water. The tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Olaparib tablets can be taken with or without food, with the exception of Day 8 (a PK sampling day) when patients aged ≥3 years old receiving tablets should take olaparib at least 1 hour after food and should refrain from eating for up to 2 hours afterwards.

- Experimental: Cohort B: ≥3 to <12 years
Patients will receive a single dose of olaparib on Day 1, followed by initiation of bd continuous dosing from Day 2 onwards. Olaparib tablets should be taken at the same time each day (morning and evening), approximately 12 hours apart with one glass of water. The tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Olaparib tablets can be taken with or without food, with the exception of Day 8 (a PK sampling day) when patients aged ≥3 years old receiving tablets should take olaparib at least 1 hour after food and should refrain from eating for up to 2 hours afterwards.

- Experimental: Cohort C: ≥6 months to <6 years
Patients will receive a single dose of olaparib on Day 1, followed by initiation of bd continuous dosing from Day 2 onwards, using the AAF when available (if required). Olaparib tablets should be taken at the same time each day (morning and evening), approximately 12 hours apart with one glass of water. The tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Olaparib tablets/AAF can be taken with or without food, with the exception of Day 8 (a PK sampling day) when patients aged ≥3 years old receiving tablets should take olaparib at least 1 hour after food and should refrain from eating for up to 2 hours afterwards.

- Experimental: Signal identification
A secondary analysis of response in patients recruited into the signal identification phase will be conducted. Patients included in this analysis must have documented evidence of a deleterious or suspected deleterious germline or tumour HRR gene mutation. A minimum of 10 patients across age and dose cohorts with deleterious or suspected deleterious HRR mutations will be enrolled.

Phase : I

Stade : Localisé à Métastasique

2, 3, 4, X
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : Key Inclusion Criteria:
- Provision of Informed Consent
- Male and female patients who are ≥6 months to <18 years of age at the screening visit.
- Pathologically confirmed relapsed or refractory non-CNS solid tumours (excluding lymphoid malignancies), with a HRR deficiency, and for whom there are no standard treatment options. Eligible patients may include but not be limited to those with osteosarcoma, rhabdomyosarcoma, non rhabdomyosarcoma soft tissue sarcoma, Ewing Sarcoma and neuroblastoma.
- For dose finding phase only: recruitment will be open to all patients with HRR deficiency, either based on a local test or by using a central germline test. For the signal identification phase: recruitment will be open only to patients with documented evidence of a deleterious or suspected deleterious germline or tumour HRR gene mutation that meets the olaparib HRR classification rules
- An FFPE tumour sample from the primary cancer (all patients) and blood sample (patients ≥2 years old) suitable for central HRR testing must be provided for each patient.
- For all non-neuroblastoma tumours, patients must have at least 1 radiographical assessable lesion (measurable and/or non-measurable). For neuroblastoma tumours, patients must have radiographical assessable disease with at least 1 lesion (measurable and/or non measurable) OR disease evidenced by uptake of meta-iodobenzylguanidine- (MIBG) or fluorodeoxyglucose positron emission tomography (FDG-PET) scans.
- Adequate performance status, organ, and marrow function and adequate weight to obtain blood samples for both safety laboratory assessments and PK analysis.
- Ability to swallow tablets

Critères de non-inclusion : Key Exclusion Criteria:
- Patients with MDS/AML or with features suggestive of MDS/AML.
- Patients unable to swallow orally administered medication
- Unresolved toxicity from previous anticancer therapy
- Unstable or untreated CNS disease (i.e., symptomatic uncontrolled brain metastases or untreated spinal cord compression)
- Previous treatment with a PARP inhibitor, including olaparib
- Receipt of any radiotherapy for cancer treatment (except for palliative reasons) within 30 days prior to first dose of study treatment or receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, monoclonal antibodies, etc) within 21 days prior to the first dose of study treatment.
- Concomitant use of known strong or moderate CYP3A inhibitors or concomitant use of known strong or moderate CYP3A inducers
- Whole blood transfusions in the last 120 days prior to screening (packed red blood cells and platelet transfusions are acceptable).
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04236414
Promoteur :
AstraZeneca
Type de sponsor : Industriel
00000 HORS FRANCE

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Oscar Lambret - 3 Rue Frédéric Combemale - 59000 LILLE

Investigateur :
Docteur Anne-Sophie DEFACHELLES

TEC / ARC / IDE :
Unité Intégrée de Recherche Clinique
investigation@
o-lambret.fr
03.20.29.59.35

Statut de l'essai : OUVERT

MAJ : 17/02/2020