Study in Children and Adolescents of 177Lu-DOTATATE (Lutathera®) Combined with the PARP Inhibitor Olaparib for the Treatment of Recurrent or Relapsed Solid Tumours Expressing Somatostatin Receptor (SSTR) (LuPARPed).

Summary

Study in children and adolescents of 177Lu DOTATATE (Lutathera®) combined with the PARP inhibitor olaparib for treatment of recurrent or relapsed solid tumours expressing somatostatin receptors (SSTR) (LuPARPed)

Eligibility

Inclusion Criteria:

* 18 months - 18 years of age at the time of the initial diagnosis.
* ≥ 3 years at the moment of inclusion in the trial.
* Diagnosis: relapsed/refractory solid tumours with positive uptake on SSTR-PET (PET-CT or PET-MRI), performed in the previous three months before entering the study. The positiveness of the study in patients with localized CNS tumours that do not spread through the spine, will be assessed according to:
* Active uptake: when the tumoral lesion shows SSTR expression higher than the one of the background cerebral uptake.
* Negative uptake: when the tumoral lesion shows no SSTR expression. Patients with active uptake in the majority of the tumoral lesions will be considered to have a positive SSTR-PET and will be therefore eligible for the trial.

For the rest of the patients, the evaluation of SSTR expression will be classified according to a qualitative 4-point scale: SSTR expression V (visual score):

* Score = 0: Below or equal to blood pool
* Score = 1: Above blood pool and lower than liver
* Score = 2: Equal to or above liver and lower than spleen
* Score = 3: Equal to or above spleen Patients with scores ≥ 2 in the majority of the tumoral lesions will be considered to have a positive SSTR-PET and will 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 of at least 3 months.
* Availability of ability to swallow tablets
* Adequate organ function within 28 days prior to enrolment, as defined by:
* Hb ≥10 g/dl (packed red blood transfusion is acceptable up to 24 hours prior starting treatment);
* White blood cell (WBC) count ≥ 2500/µL (equivalent to 2.5 x 109/L)
* Absolute Neutrophil Count (ANC) ≥ 1000/µl;
* Platelets ≥ 50.000/µl, without transfusion in the prior ≥10 days;
* Serum plasma creatinine ≤ 1.5 x upper limit of normal (ULN) OR estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2 (assessed by 2009-Schwartz formula).
* Total bilirubin ≤ 1.5 x the institutional ULN. For patients with known Gilbert's Syndrome ≤ 3.0 ULN is permitted.
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 3.0 ULN OR ≤ 5.0 ULN for patients with liver metastases.
* Albumin \>3.0 g/dL (3.0 g/dL is equivalent to 30 g/L)
* A negative serum or urine pregnancy test in women with onset of menses or \>12 years of age.
* Patients of reproductive potential must agree to use highly effective contraceptive methods for the entire study duration and up to 7 months, in case of females, and 4 months in case of males, after the last dose of Lutathera, or up to 6 months, in case of females, and 3 months in case of males, after the last dose of olaparib, whichever takes places later.
* Have the ability to comprehend and willingness to provide written informed consent (ICF) for the study before patient registration or any trial-related screening procedures. If the patient is \<18 years old, the written informed consent must be signed by the parent(s) or legal guardian(s) according to national regulations. In the case of patients between 12 and 17 years, they must sign an assent form, and if the patient turns 18 during their participation in the study, they must sign an informed consent form.
* Adequate recovery from major surgery prior to receiving study treatment.
* Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Exclusion Criteria:

* Having received more than one previous treatment with other radiolabelled somatostatin analogues.
* Inability to swallow tablets.
* Subjects who are currently receiving any other anticancer and/or investigational agents. There must be at least two-week of washout from any prior treatment.
* Treatment with long-acting somatostatin analogues within 30 days prior the administration of 177Lu-DOTATATE.
* Known hypersensitivity to any of the excipients.
* Subjects who have an uncontrolled infection.
* Lactating women.

Conditions10

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