Primary Outcomes

Measure: genetic factors (drug metabolism enzymes, membrane transporters) predisposing to cisplatin and carboplatin ototoxicity in children

Time: Day 0

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Secondary Outcomes

Measure: genetic factors predisposing to aminoglycoside ototoxicity;

Time: Day 0

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Measure: To provide a rationale for prevention of ototoxicity by the use of antioxidant medications.

Time: Day 0

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Primary Outcomes

Measure: Investigation of the change in the tumour Ki-67 before and after treatment with the combination of olaparib + durvalumab or olaparib + cisplatin or olaparib monotherapy.

Time: At baseline and at the day of the surgery or 2nd biopsy (at days 23-29 days)

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Secondary Outcomes

Measure: Objective response rate according to RECIST 1.1 criteria

Time: Imaging studies will be performed at baseline and on week 4

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Measure: Pathologic complete response rate

Time: On week 4 only for operable patients

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Measure: Metabolic response rate assessed by FDG-PET/CT scan (optional)

Time: At baseline, on week 4

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Measure: Number of participants with tolerability to the treatment.

Time: From the 1st day of therapy and every week for 4 weeks maximum and 90 days after last therapy administration

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Measure: Surgical complication rate

Time: Up to 30 days after surgery or the day of initiation of the next anticancer therapy

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Measure: Mutations in genes associated with DNA repair

Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

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Measure: Expression of tissue biomarker: PARP1

Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

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Measure: Expression of tissue biomarker: BRACA1,2

Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

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Measure: Expression of tissue biomarker: ERCC1

Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

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Measure: Expression of tissue biomarker: PDL-1

Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

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Measure: Expression of tissue biomarker: TILs

Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)

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Measure: Plasma methylation biomarker: PARP1 methylation in plasma cell-free DNA

Time: At baseline, a day before surgery and 90 days after surgery

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Measure: Plasma methylation biomarker: BRCA1,2 methylation in plasma cell-free DNA

Time: At baseline, a day before surgery and 90 days after surgery

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Measure: Plasma methylation biomarker: ERCC1 methylation in plasma cell-free DNA

Time: At baseline, a day before surgery and 90 days after surgery

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Measure: Plasma methylation biomarker: RAD51C methylation in plasma cell-free DNA

Time: At baseline, a day before surgery and 90 days after surgery

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Measure: Single-nucleotide polymorphisms: PARP-1 Val762Ala

Time: Sample will be collected once at baseline

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Measure: Single-nucleotide polymorphisms: ERCC1 Asn118Asn (C/T)

Time: Sample will be collected once at baseline

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Measure: Single-nucleotide polymorphisms:ERCC2 Lys751Gln (T/G)

Time: Sample will be collected once at baseline

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Measure: Single-nucleotide polymorphisms: GSTP1 Ile105Val (A/G)

Time: Sample will be collected once at baseline

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Measure: Single-nucleotide polymorphisms: XPD Lys751Gln (A/C, C/C)

Time: Sample will be collected once at baseline

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Measure: Single-nucleotide polymorphisms: XRCC1 Arg399Gln (G/A)

Time: Sample will be collected once at baseline

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Measure: Circulating tumor cells (CTCs) evaluated for DNA repair biomarkers

Time: At baseline, a day before surgery and 90 days after surgery

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Measure: Circulating tumor cells (CTCs) evaluated for PD-L1

Time: At baseline, a day before surgery and 90 days after surgery

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