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Trial record 1 of 1 for:    D0816C00025
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Investigating Safety, Tolerability, Efficacy and PK of Olaparib in Paediatric Patients With Solid Tumours

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ClinicalTrials.gov Identifier: NCT04236414
Recruitment Status : Recruiting
First Posted : January 22, 2020
Last Update Posted : March 26, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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

Condition or disease Intervention/treatment Phase
Solid Tumours Drug: Olaparib Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 14, 2020
Estimated Primary Completion Date : December 30, 2025
Estimated Study Completion Date : December 30, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Olaparib

Arm Intervention/treatment
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 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.

25 and 100 mg tablet strengths available for ages ≥3 to <18 years. Feasibility for an AAF for ≥0.5 to <6 years planned.


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 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.

25 and 100 mg tablet strengths available for ages ≥3 to <18 years. Feasibility for an AAF for ≥0.5 to <6 years planned.


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, using the AAF when available (if required). 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/AAF 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 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.

25 and 100 mg tablet strengths available for ages ≥3 to <18 years. Feasibility for an AAF for ≥0.5 to <6 years planned.


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 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.

25 and 100 mg tablet strengths available for ages ≥3 to <18 years. Feasibility for an AAF for ≥0.5 to <6 years planned.





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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04236414


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Denmark
Research Site Recruiting
København Ø, Denmark, 2100
France
Research Site Recruiting
Lille, France, 59000
Research Site Recruiting
Marseille, France, 13005
Research Site Recruiting
Paris, France, 75005
Research Site Recruiting
Toulouse, France, 31300
Research Site Recruiting
Villejuif, France, 94800
Germany
Research Site Recruiting
Heidelberg, Germany, 69120
Research Site Recruiting
Mainz A. Rhein, Germany, 55131
Israel
Research Site Recruiting
Haifa, Israel, 3109601
Research Site Recruiting
Petah Tikva, Israel, 4920235
Korea, Republic of
Research Site Recruiting
Seoul, Korea, Republic of, 03080
Research Site Recruiting
Seoul, Korea, Republic of, 06351
Research Site Recruiting
Songpa-gu, Korea, Republic of, 05505
Spain
Research Site Recruiting
Barcelona, Spain, 08035
Research Site Recruiting
Esplugues De Llobregat (Barc), Spain, 08950
Research Site Recruiting
Madrid, Spain, 28009
Research Site Recruiting
Madrid, Spain, 28046
Research Site Recruiting
Valencia, Spain, 46026
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 Not yet recruiting
Sutton, United Kingdom, SM2 5PT
Sponsors and Collaborators
AstraZeneca
Investigators
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Study Director: Milenkova Tsveta AstraZeneca
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04236414    
Other Study ID Numbers: D0816C00025
2018-003355-38 ( EudraCT Number )
First Posted: January 22, 2020    Key Record Dates
Last Update Posted: March 26, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 Materials: 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Cancer
Malignant cancer
Paediatric population
Olaparib
Additional relevant MeSH terms:
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Neoplasms
Olaparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents