Study in children and adolescents for the treatment of recurrent or relapsed solid tumours with the treatment of Lutathera® combined with olaparib Proposed

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion De investigacion De Hm Hospitales

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

28 Aug 2024 → ongoing

Decision date (initial)

2024-08-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Phase I:• To estimate the maximum tolerated dose (MTD) and select thepaediatric RP2D of the combination of 177LUDOTATATE andolaparib.• To determine the preliminary antitumor activity of the combinationof 177LUDOTATATE and olaparib.• To determine the impact on the quality of life of the combination of177LUDOTATATE and olaparib.• To determine the SSRT expression by IHC in R/R solid tumours onthe original pathological specimen.
Phase II: • To determine the safety, tolerability and activity of therapy with177Lu-DOTATATE and olaparib.• To determine the frequency of treatment reductions, need of drugholidays and delays on treatment administration.• To determine the impact on the quality of life of the combination of177LUDOTATATE and olaparib.• To determine the SSTR expression by IHC in R/R solid tumour onthe original pathological specimen.

Secondary objectives 1

1. To determine and/or describe: Disease Control Rate (DCR), measured by RECIST v1.122/ INRC23,24/RAPNO25-29. • Duration of response (DOR). • Time to response (TTR). • Progression-free survival (PFS). • Overall-survival (OS). • (S)AEs assessment by CTAE v5.0. • Frequency of dose reductions, need of drug holidays and delays on treatment administration. • Impact on the quality of life of the combination of 177LUDOTATATE and olaparib

Conditions and MedDRA coding

Recurrent or relapsed solid tumours expressing somatostatin receptors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. - 18 months – 18 years of age at the time of the initial diagnosis.- ≥ 3 years old at the moment of inclusion in the trial.Diagnosis: relapsed/refractory solid tumours with positive uptake on SSRT-PET (PET-CT or PET-MRI), performed in the previous three months before entering in the study. The evaluation of SSTR expression will be classified according to a qualitative 4-point scale: SSTR expression V (visual score):o Score = 0: Below or equal to blood poolo Score = 1: Above blood pool and lower than livero Score = 2: Equal to or above liver and lower than spleeno Score = 3: Equal to or above spleenPatients should have scores ≥ 2 in the majority of the tumoral lesions to be considered to have a positive SSTR-PET and be therefore eligible for the trial. Patients with a higher score are presumed to have a better response to the treatment.It is admissible to have non-measurable disease only (e.g. HR-NB with bone-only or bone-marrow-only active disease)- Performance status ≥ 50% according to Lansky scale (<16 years old)or Karnofsky scale (for ≥16 years old)- Life expectancy ≥ 3 months.- Availability of ability to swallow tablets or capsules.- Adequate function within 28 days prior to enrolment, as defined by:o Hb ≥10 g/dl (packed red blood transfusion is acceptable upto 24 hours prior starting treatment);o White blood cell (WBC) count ≥ 2500/µL (equivalent to 2.5x 109/L) o Absolute Neutrophil Count (ANC) ≥ 1000/µl (equivalent to≥ 1 x 109/L)o Platelets ≥ 100.000/µl (equivalent to ≥100.0 x 109/L),without transfusion in the prior ≥7 days.o Serum plasma creatinine ≤ 1.5 x upper limit of normal (ULN)OR estimated glomerular filtration rate (eGFR) ≥ 60mL/min/1.73m2 (assessed by 2009-Schwartz formula)o Total bilirubin ≤ 1.5 x the institutional ULN. For patientswith known Gilbert’s Syndrome ≤ 3.0 ULN is permittedo Alanine aminotransferase (ALT) or aspartateaminotransferase (AST) ≤ 3.0 ULNo Albumin ≥3.0 g/dL (equivalent to ≥30 g/L) - A negative serum or urine pregnancy test in women with onset ofmenses and/or ≥12 years of age- Patients of reproductive potential must agree to use highly effectivecontraceptive methods for the entire study duration and up to 7months, in case of females, and 4 months in case of males, after thelast dose of Lutathera, or up to 6 months, in case of females, and 3months in case of males, after the last dose of olaparib, whichevertakes places later.- Have the ability to comprehend and willingness to provide writteninformed consent (ICF) for the study before patient registration orany trial-related screening procedures. If the patient is <18 years old,the written informed consent must be signed by the parent(s) or legalguardian(s) according to national regulations. In the case of patientsbetween 12 and 17 years, they must sign an assent form, and if thepatient turns 18 during their participation in the study, they must signan informed consent form.- Absence of any psychological, familial, sociological or geographicalcondition potentially hampering compliance with the study protocoland follow-up schedule; those conditions should be discussed withthe patient before registration in the trial.- Adequate recovery from major surgery prior to receiving study treatment.

Exclusion criteria 1

1. Previous significant drug-induced hepatitis toxicity experienced inthe past that has required treatment dose reductions, treatmentdiscontinuation or that, at the investigator discretion, could infer arisk.- Having received more than one previous treatment with otherradiolabeled somatostatin analogues.- Inability to swallow tablets or capsules.- Subjects who are currently receiving any other anticancer and/orinvestigational agents (e.g. chemotherapy, immunotherapy orbiological therapy [including monoclonal antibodies]). There must beat least 28 days of washout from any prior treatment. In case ofcheckpoint inhibitors, there should be at least 4 months of washout.Palliative Radiation Therapy for symptom control (e.g. pain relief)could be acceptable, at discretion of the investigator.- Treatment with long-acting somatostatin analogues within 28 daysprior the administration of 177Lu-DOTATATE- Known hypersensitivity to any of the excipients.- Subjects who have an uncontrolled infection.- Lactating women.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary endpoint of this study is objective tumour response. Tumour response is defined by RECIST v1.122 as complete response, partial response, stable response and progressive disease (for further details refer to the Appendix E or the publication22).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion De investigacion De Hm Hospitales

Sponsor organisation

Fundacion De investigacion De Hm Hospitales

Address

Plaza Del Conde Del Valle De Suchil 2

City

Madrid

Postcode

28015

Country

Spain

Scientific contact point

Organisation

Fundacion De investigacion De Hm Hospitales

Contact name

Francisco Aldea

Public contact point

Organisation

Fundacion De investigacion De Hm Hospitales

Contact name

Francisco Aldea

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

3 submissions — initial application plus substantial / non-substantial modifications