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JOURNAL ONKOLOGIE – STUDIE

Investigating Safety, Tolerability, Efficacy and PK of Olaparib in Paediatric Patients With Solid Tumours

Rekrutierend

NCT-Nummer:
NCT04236414

Studienbeginn:
Januar 2020

Letztes Update:
08.02.2024

Wirkstoff:
Olaparib

Indikation (Clinical Trials):
Neoplasms

Geschlecht:
Alle

Altersgruppe:
Kinder (0-17)

Phase:
Phase 1

Sponsor:
AstraZeneca

Collaborator:
-

Studienleiter

Milenkova Tsveta
Study Director
AstraZeneca

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com» Kontaktdaten anzeigen

Studienlocations
(3 von 44)

Research Site
69120 Heidelberg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Research Site
55131 Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps
Research Site
44106 Cleveland
United StatesNoch nicht rekrutierend» Google-Maps
Research Site
197022 Saint Petersburg
Russian FederationZurückgezogen» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

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 solid or primary CNS tumours (excluding lymphoid

malignancies) 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, neuroblastoma, medulloblastoma and

glioma

Ein-/Ausschlusskriterien

Key Inclusion Criteria:

- Provision of Informed Consent

- Male and female patients who are ≥6 months to <18 years of age at consent

- Pathologically confirmed relapsed or refractory solid or primary CNS tumours

(excluding lymphoid malignancies), with a HRR deficiency/gene mutation, 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, neuroblastoma, medulloblastoma and glioma

- For dose finding phase only: recruitment will be open to all patients with HRR

deficiency, based on a local 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 AZ HRR rules

- A formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer (all

patients) suitable for central HRR testing and a blood sample (patients ≥2 years old)

for central germline BRCA 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

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)

Studien-Rationale

Primary outcome:

1. Dose limiting toxicity [DLTs] (Time Frame - 28 days):
DLT - Dose limiting toxicity

2. Safety profile (Time Frame - Until 30 days after last dose):
Number of patients with adverse events

Secondary outcome:

1. Apparent total clearance of the drug from plasma at steady state after oral administration [CLss/F] (Time Frame - The pre-dose sample should be collected within 12±0.5 hours of the Day 7 evening dose of olaparib, prior to the Day 8 morning dose and within 12±1 hours of the Day 28 evening olaparib dose, prior to the Day 29 morning dose.):
Olaparib levels in mcg/mL

2. Maximum plasma concentration at steady state [Css,max] (Time Frame - The pre-dose sample should be collected within 12±0.5 hours of the Day 7 evening dose of olaparib, prior to the Day 8 morning dose and within 12±1 hours of the Day 28 evening olaparib dose, prior to the Day 29 morning dose.):
Olaparib levels in mcg/mL

3. Minimum plasma concentration at steady state [Css, min] (Time Frame - The pre-dose sample should be collected within 12±0.5 hours of the Day 7 evening dose of olaparib, prior to the Day 8 morning dose and within 12±1 hours of the Day 28 evening olaparib dose, prior to the Day 29 morning dose.):
Olaparib levels in mcg/mL

4. Time to maximum plasma concentration at steady state [tss,max] (Time Frame - The pre-dose sample should be collected within 12±0.5 hours of the Day 7 evening dose of olaparib, prior to the Day 8 morning dose and within 12±1 hours of the Day 28 evening olaparib dose, prior to the Day 29 morning dose.):
Olaparib levels in mcg/mL

5. Area under the curve at steady state [AUCss] (Time Frame - The pre-dose sample should be collected within 12±0.5 hours of the Day 7 evening dose of olaparib, prior to the Day 8 morning dose and within 12±1 hours of the Day 28 evening olaparib dose, prior to the Day 29 morning dose.):
Olaparib levels in mcg/mL

6. Dose normalised area under the curve at steady state [dose normalised AUCss] (Time Frame - The pre-dose sample should be collected within 12±0.5 hours of the Day 7 evening dose of olaparib, prior to the Day 8 morning dose and within 12±1 hours of the Day 28 evening olaparib dose, prior to the Day 29 morning dose.):
Olaparib levels in mcg/mL

7. Area under the curve at 0-8 hours [AUC(0-8)] (Time Frame - The pre-dose sample should be collected within 12±0.5 hours of the Day 7 evening dose of olaparib, prior to the Day 8 morning dose and within 12±1 hours of the Day 28 evening olaparib dose, prior to the Day 29 morning dose.):
Olaparib levels in mcg/mL

8. Area under the curve from zero up to time t [AUC0-t] (Time Frame - The pre-dose sample should be collected within 12±0.5 hours of the Day 7 evening dose of olaparib, prior to the Day 8 morning dose and within 12±1 hours of the Day 28 evening olaparib dose, prior to the Day 29 morning dose.):
Olaparib levels in mcg/mL

9. Dose normalised maximum plasma concentration at steady state [dose normalised Css,max] (Time Frame - The pre-dose sample should be collected within 12±0.5 hours of the Day 7 evening dose of olaparib, prior to the Day 8 morning dose and within 12±1 hours of the Day 28 evening olaparib dose, prior to the Day 29 morning dose.):
Olaparib levels in mcg/mL

10. ORR as defined by Investigator-assessed RECIST v1.1, INRC or RANO (Time Frame - Up to 64 months):
ORR - Objective response rate INRC - International Neuroblastoma Response Criteria RECIST - Response Evaluation Criteria in Solid tumours RANO - Response Assessment in Neuro-oncology

11. DCR as defined by Investigator-assessed RECIST v1.1, INRC or RANO (Time Frame - Up to 64 months):
DCR - Disease control rate INRC - International Neuroblastoma Response Criteria RECIST - Response Evaluation Criteria in Solid tumours RANO - Response Assessment in Neuro-oncology

12. DoR as defined by Investigator-assessed RECIST v1.1, INRC or RANO (Time Frame - Up to 64 months):
DoR - Duration of response INRC - International Neuroblastoma Response Criteria RECIST - Response Evaluation Criteria in Solid tumours RANO - Response Assessment in Neuro-oncology

Studien-Arme

  • 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. Olaparib should be taken at the same time each day (morning and evening), approximately 12 hours apart. Patients in Cohort C will receive a predetermined number of each sprinkle capsule strength (15 and 19.5 mg,) to make up the required dose. Olaparib sprinkle capsules will be administered to the child by the parent/caregiver. Patients in Cohort C are not required to fast including PK sampling days. The dispensed granules should be swallowed whole and not chewed, crushed, dissolved or divided, and should be consumed within 30 minutes of preparation.
  • 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.

Geprüfte Regime

  • Olaparib:
    Patients will receive a single dose of olaparib on Day 1, followed by initiation of bd continuous dosing from Day 2 onwards. Olaparib 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. 25 and 100 mg tablet strengths available for ages ≥3 to <18 years. AAF available for ≥0.5 to <6 years; The AAF is a sprinkle capsule formulation, available in dose strengths of 15 mg and 19.5 mg. The sprinkle capsules contain 1.5 mg granules which are to be dispersed onto a food vehicle prior to dosing.

Quelle: ClinicalTrials.gov


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