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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04236414




Registration number
NCT04236414
Ethics application status
Date submitted
13/11/2019
Date registered
22/01/2020

Titles & IDs
Public title
Investigating Safety, Tolerability, Efficacy and PK of Olaparib in Paediatric Patients With Solid Tumours
Scientific title
A Phase I, Open-label, Parallel Group Study to Investigate Olaparib Safety and Tolerability, Efficacy and Pharmacokinetics in Paediatric Patients With Solid Tumours
Secondary ID [1] 0 0
2018-003355-38
Secondary ID [2] 0 0
D0816C00025
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumours 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Olaparib

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.


Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose limiting toxicity [DLTs]
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Safety profile
Timepoint [2] 0 0
Until 30 days after last dose
Secondary outcome [1] 0 0
Apparent total clearance of the drug from plasma at steady state after oral administration [CLss/F]
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Maximum plasma concentration at steady state [Css,max]
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Minimum plasma concentration at steady state [Css, min]
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Time to maximum plasma concentration at steady state [tss,max]
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Area under the curve at steady state [AUCss]
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Dose normalised area under the curve at steady state [dose normalised AUCss]
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Area under the curve at 0-8 hours [AUC(0-8)]
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
Area under the curve from zero up to time t [AUC0-t]
Timepoint [8] 0 0
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.
Secondary outcome [9] 0 0
Dose normalised maximum plasma concentration at steady state [dose normalised Css,max]
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
ORR as defined by Investigator-assessed RECIST v1.1, INRC or RANO
Timepoint [10] 0 0
Up to 64 months
Secondary outcome [11] 0 0
DCR as defined by Investigator-assessed RECIST v1.1, INRC or RANO
Timepoint [11] 0 0
Up to 64 months
Secondary outcome [12] 0 0
DoR as defined by Investigator-assessed RECIST v1.1, INRC or RANO
Timepoint [12] 0 0
Up to 64 months

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
0 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/01/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/12/2025
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Clayton
Recruitment hospital [2] 0 0
Research Site - Nedlands
Recruitment hospital [3] 0 0
Research Site - Randwick
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
6009 - Nedlands
Recruitment postcode(s) [3] 0 0
2031 - Randwick
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
South Carolina
Country [5] 0 0
Austria
State/province [5] 0 0
Wien
Country [6] 0 0
Brazil
State/province [6] 0 0
Natal
Country [7] 0 0
Brazil
State/province [7] 0 0
Sao Paulo
Country [8] 0 0
Canada
State/province [8] 0 0
Alberta
Country [9] 0 0
Canada
State/province [9] 0 0
British Columbia
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
Denmark
State/province [12] 0 0
København Ø
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
France
State/province [14] 0 0
Marseille
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
France
State/province [16] 0 0
Toulouse
Country [17] 0 0
France
State/province [17] 0 0
Villejuif Cedex
Country [18] 0 0
Germany
State/province [18] 0 0
Heidelberg
Country [19] 0 0
Germany
State/province [19] 0 0
Mainz
Country [20] 0 0
Hungary
State/province [20] 0 0
Budapest
Country [21] 0 0
Israel
State/province [21] 0 0
Haifa
Country [22] 0 0
Israel
State/province [22] 0 0
Petah Tikva
Country [23] 0 0
Italy
State/province [23] 0 0
Roma
Country [24] 0 0
Korea, Republic of
State/province [24] 0 0
Seoul
Country [25] 0 0
Poland
State/province [25] 0 0
Szczecin
Country [26] 0 0
Poland
State/province [26] 0 0
Warszawa
Country [27] 0 0
Russian Federation
State/province [27] 0 0
Moscow
Country [28] 0 0
Russian Federation
State/province [28] 0 0
Saint Petersburg
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Spain
State/province [31] 0 0
Valencia
Country [32] 0 0
Ukraine
State/province [32] 0 0
Dnipro
Country [33] 0 0
Ukraine
State/province [33] 0 0
Lviv
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Birmingham
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Glasgow
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Leeds
Country [37] 0 0
United Kingdom
State/province [37] 0 0
Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Milenkova Tsveta
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
information.center@astrazeneca.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data assessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04236414