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

Solid Tumours Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04236414
• Other study ID #: D0816C00025
• Secondary ID: 2018-003355-38
• Status: Recruiting
• Phase: Phase 1
• Start date: January 14, 2020
• Est. completion date: December 30, 2025

Study information

• Verified date: February 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 30, 2025
• Est. primary completion date: December 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 18 Years

Eligibility

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)

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumours

Intervention

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.

Locations

Country	Name	City	State
Australia	Research Site	Clayton
Australia	Research Site	Nedlands
Australia	Research Site	Randwick
Austria	Research Site	Wien
Brazil	Research Site	Natal
Brazil	Research Site	Sao Paulo
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Denmark	Research Site	København Ø
France	Research Site	Lille
France	Research Site	Marseille
France	Research Site	Paris
France	Research Site	Toulouse
France	Research Site	Villejuif Cedex
Germany	Research Site	Heidelberg
Germany	Research Site	Mainz
Hungary	Research Site	Budapest
Israel	Research Site	Haifa
Israel	Research Site	Petah Tikva
Italy	Research Site	Roma
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Poland	Research Site	Szczecin
Poland	Research Site	Warszawa
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Valencia
Ukraine	Research Site	Dnipro
Ukraine	Research Site	Lviv
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Sutton
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Cleveland	Ohio
United States	Research Site	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Brazil,  Canada,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity [DLTs]	DLT - Dose limiting toxicity	28 days
Primary	Safety profile	Number of patients with adverse events	Until 30 days after last dose
Secondary	Apparent total clearance of the drug from plasma at steady state after oral administration [CLss/F]	Olaparib levels in mcg/mL	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	Maximum plasma concentration at steady state [Css,max]	Olaparib levels in mcg/mL	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	Minimum plasma concentration at steady state [Css, min]	Olaparib levels in mcg/mL	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	Time to maximum plasma concentration at steady state [tss,max]	Olaparib levels in mcg/mL	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	Area under the curve at steady state [AUCss]	Olaparib levels in mcg/mL	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	Dose normalised area under the curve at steady state [dose normalised AUCss]	Olaparib levels in mcg/mL	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	Area under the curve at 0-8 hours [AUC(0-8)]	Olaparib levels in mcg/mL	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	Area under the curve from zero up to time t [AUC0-t]	Olaparib levels in mcg/mL	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	Dose normalised maximum plasma concentration at steady state [dose normalised Css,max]	Olaparib levels in mcg/mL	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	ORR as defined by Investigator-assessed RECIST v1.1, INRC or RANO	ORR - Objective response rate INRC - International Neuroblastoma Response Criteria RECIST - Response Evaluation Criteria in Solid tumours RANO - Response Assessment in Neuro-oncology	Up to 64 months
Secondary	DCR as defined by Investigator-assessed RECIST v1.1, INRC or RANO	DCR - Disease control rate INRC - International Neuroblastoma Response Criteria RECIST - Response Evaluation Criteria in Solid tumours RANO - Response Assessment in Neuro-oncology	Up to 64 months
Secondary	DoR as defined by Investigator-assessed RECIST v1.1, INRC or RANO	DoR - Duration of response INRC - International Neuroblastoma Response Criteria RECIST - Response Evaluation Criteria in Solid tumours RANO - Response Assessment in Neuro-oncology	Up to 64 months