ClinicalTrials.gov
History of Changes for Study: NCT04236414
Investigating Safety, Tolerability, Efficacy and PK of Olaparib in Paediatric Patients With Solid Tumours
Latest version (submitted February 7, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 21, 2020 None (earliest Version on record)
2 March 5, 2020 Study Status and Contacts/Locations
3 May 28, 2020 Study Status and IPDSharing
4 July 29, 2020 Eligibility, Outcome Measures, Study Status, Contacts/Locations and Study Description
5 August 25, 2020 Study Status and Study Design
6 October 2, 2020 Study Status, Contacts/Locations and Eligibility
7 November 12, 2020 Oversight and Study Status
8 December 16, 2020 Study Status and Contacts/Locations
9 January 18, 2021 Study Status and Contacts/Locations
10 February 25, 2021 Study Status and Contacts/Locations
11 March 25, 2021 Study Status
12 May 26, 2021 Study Status and Contacts/Locations
13 June 21, 2021 Study Status
14 July 20, 2021 Study Status and Study Description
15 August 26, 2021 Contacts/Locations and Study Status
16 September 21, 2021 Study Status
17 October 22, 2021 Study Status
18 November 25, 2021 Study Status and Study Description
19 December 23, 2021 Study Status
20 January 28, 2022 Contacts/Locations and Study Status
21 February 28, 2022 Study Status
22 April 21, 2022 Arms and Interventions, Study Status and Contacts/Locations
23 May 23, 2022 Study Status and Study Description
24 July 26, 2022 Study Status
25 September 1, 2022 Contacts/Locations and Study Status
26 September 30, 2022 Study Status
27 November 7, 2022 Contacts/Locations and Study Status
28 December 2, 2022 Study Status and Contacts/Locations
29 February 8, 2023 Study Status and Contacts/Locations
30 March 17, 2023 Study Status and Contacts/Locations
31 June 30, 2023 Contacts/Locations and Study Status
32 November 24, 2023 Contacts/Locations and Study Status
33 January 5, 2024 Study Status and Contacts/Locations
34 February 7, 2024 Study Status
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Study NCT04236414
Submitted Date:  November 7, 2022 (v27)
Open or close this module Study Identification
Unique Protocol ID: D0816C00025
Brief Title: Investigating Safety, Tolerability, Efficacy and PK of Olaparib in Paediatric Patients With Solid Tumours
Official 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 IDs: 2018-003355-38 [EudraCT Number]
Open or close this module Study Status
Record Verification: November 2022
Overall Status: Recruiting
Study Start: January 14, 2020
Primary Completion: December 30, 2025 [Anticipated]
Study Completion: December 30, 2025 [Anticipated]
First Submitted: November 13, 2019
First Submitted that
Met QC Criteria:		 January 21, 2020
First Posted: January 22, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:		 November 7, 2022
Last Update Posted: November 8, 2022 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: AstraZeneca
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
Brief Summary: A study to find out whether olaparib is safe and well tolerated when administered to children and adolescents with solid tumours.
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
Open or close this module Conditions
Conditions: Solid Tumours
Keywords: Cancer
Malignant cancer
Paediatric population
Olaparib
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Parallel Assignment
Number of Arms: 4
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 30 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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.
 Drug: 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.
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.
 Drug: 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.
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.
 Drug: 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.
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.
 Drug: 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.
Open or close this module Outcome Measures
Primary Outcome Measures:
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 Measures:
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
Open or close this module Eligibility
Minimum Age: 0 Years
Maximum Age: 18 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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)
Open or close this module Contacts/Locations
Central Contact Person: AstraZeneca Clinical Study Information Center
Telephone: 1-877-240-9479
Email: information.center@astrazeneca.com
Study Officials: Milenkova Tsveta
Study Director
AstraZeneca
Locations: United States, North Carolina
Research Site
[Not yet recruiting]
Charlotte, North Carolina, United States, 28203
Australia
Research Site
[Withdrawn]
Clayton, Australia, 3168
Research Site
[Not yet recruiting]
Nedlands, Australia, 6009
Research Site
[Not yet recruiting]
Randwick, Australia, 2031
Canada, Quebec
Research Site
[Not yet recruiting]
Montreal, Quebec, Canada, H4A 3J1
Denmark
Research Site
[Recruiting]
København Ø, Denmark, 2100
France
Research Site
[Recruiting]
Lille, France, 59000
Research Site
[Recruiting]
Marseille, France, 13385
Research Site
[Recruiting]
Paris, France, 75005
Research Site
[Recruiting]
Toulouse, France, 31300
Research Site
[Recruiting]
Villejuif Cedex, France, 94805
Germany
Research Site
[Recruiting]
Heidelberg, Germany, 69120
Research Site
[Recruiting]
Mainz A. Rhein, Germany, 55131
Hungary
Research Site
[Not yet recruiting]
Budapest, Hungary, 1094
Israel
Research Site
[Recruiting]
Haifa, Israel, 3109601
Research Site
[Recruiting]
Petah Tikva, Israel, 4920235
Italy
Research Site
[Not yet recruiting]
Roma, Italy, 00165
Korea, Republic of
Research Site
[Recruiting]
Seoul, Korea, Republic of, 03080
Research Site
[Recruiting]
Seoul, Korea, Republic of, 05505
Research Site
[Recruiting]
Seoul, Korea, Republic of, 06351
Poland
Research Site
[Suspended]
Warszawa, Poland, 01-211
Russian Federation
Research Site
[Withdrawn]
Moscow, Russian Federation, 117198
Research Site
[Withdrawn]
Saint Petersburg, Russian Federation, 197022
Spain
Research Site
[Recruiting]
Barcelona, Spain, 08035
Research Site
[Recruiting]
Barcelona, Spain, 08950
Research Site
[Recruiting]
Madrid, Spain, 28009
Research Site
[Recruiting]
Madrid, Spain, 28046
Research Site
[Recruiting]
Valencia, Spain, 46026
Ukraine
Research Site
[Withdrawn]
Lviv, Ukraine, 79035
Research Site
[Withdrawn]
Moscow, Ukraine, 117198
United Kingdom
Research Site
[Recruiting]
Birmingham, United Kingdom, B4 6NH
Research Site
[Recruiting]
Glasgow, United Kingdom, G51 4TF
Research Site
[Recruiting]
Leeds, United Kingdom, LS1 3EX
Research Site
[Recruiting]
Sutton, United Kingdom, SM2 5PT
Open or close this module IPDSharing
Plan to Share IPD: Yes
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 Information:
Study Protocol
Statistical Analysis Plan (SAP)
Time Frame:
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
Access Criteria:
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
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home
Open or close this module References
Citations:
Links:
Available IPD/Information:
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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services