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

NCT04236414 | Completed Phase 1 FDA Drug

• 3 other identifiers: D0816C000252023-507904-30-002018-003355-38
• Study Type: interventional
• Target: 16
• Locations: 6 countries
• Sites: 10

Brief Summary

A study to find out whether olaparib is safe and well tolerated when administered to children and adolescents with solid tumours.

Conditions

Solid Tumours

Keywords

Cancer; Malignant cancer; Paediatric population; Olaparib

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity [DLTs]

  DLT - Dose limiting toxicity

  28 days

• Safety profile

  Number of patients with adverse events

  Until 30 days after last dose

Secondary Outcomes (12)

• Apparent total clearance of the drug from plasma at steady state after oral administration [CLss/F]

  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.

• Maximum plasma concentration at steady state [Css,max]

  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.

• Minimum plasma concentration at steady state [Css, min]

  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.

• Time to maximum plasma concentration at steady state [tss,max]

  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.

• Area under the curve at steady state [AUCss]

  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.

Study Arms (4)

Cohort A: ≥12 to <18 years

EXPERIMENTAL

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

Cohort B: ≥3 to <12 years

EXPERIMENTAL

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

Cohort C: ≥6 months to <6 years

EXPERIMENTAL

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

Signal identification

EXPERIMENTAL

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

Interventions

Olaparib DRUG

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.

Cohort A: ≥12 to <18 years; Cohort B: ≥3 to <12 years; Cohort C: ≥6 months to <6 years; Signal identification

Eligibility Criteria

• Age: 0 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (10)

Research Site

København Ø, 2100, Denmark

Location

Research Site

Lille, 59000, France

Location

Research Site

Toulouse, 31300, France

Location

Research Site

Villejuif, 94805, France

Location

Research Site

Heidelberg, 69120, Germany

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 05505, South Korea

Location

Research Site

Madrid, 28009, Spain

Location

Research Site

Glasgow, G51 4TF, United Kingdom

Location

Research Site

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

olaparib

Study Officials

• Milenkova Tsveta

  AstraZeneca

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: January 22, 2020
• Study Start: January 14, 2020
• Primary Completion: February 4, 2025
• Study Completion: February 4, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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

Locations

KR (2); ES (1); DK (1); GB (2); DE (1); FR (3)