SNPMiner Trials (Home Page)
Report for Clinical Trial NCT02882308
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
OPHELIA (OPHELIA (OlaParib and durvalumab in HEad and neck squamous celL carcInomA) trial is
a Greek, investigator-initiated, randomized open-label window-of-opportunity phase II study.
Patients with operable histologically documented squamous-cell carcinoma of the oral cavity,
oropharynx, hypopharynx or larynx will be randomized between combination with durvalumab and
olaparib, cisplatin and olaparib, monotherapy with olaparib or no treatment, before starting
standard treatment.
Name: Olaparib
Description: 50/25 mg BD split x 5 daysType: Drug
Combination of cisplatin and olaparib
Name: Cisplatin
Description: 60 mg/m^2 d1-d5Type: Drug
Combination of cisplatin and olaparib
Name: Olaparib
Description: 300 mg BD x 21-28 days.Type: Drug
Combination of durvalumab and olaparib Monotherapy with olaparib
Name: Durvalumab
Description: 1500 mg d1Type: Drug
Combination of durvalumab and olaparib
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)
Secondary Outcomes
Measure: Objective response rate according to RECIST 1.1 criteria
Time: Imaging studies will be performed at baseline and on week 4
Measure: Pathologic complete response rate
Time: On week 4 only for operable patients
Measure: Metabolic response rate assessed by FDG-PET/CT scan (optional)
Time: At baseline, on week 4
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
Measure: Surgical complication rate
Time: Up to 30 days after surgery or the day of initiation of the next anticancer therapy
Measure: Mutations in genes associated with DNA repair
Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Expression of tissue biomarker: PARP1
Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Expression of tissue biomarker: BRACA1,2
Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Expression of tissue biomarker: ERCC1
Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Expression of tissue biomarker: PDL-1
Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Expression of tissue biomarker: TILs
Time: At baseline, on day of surgery or the 2nd biopsy (at days 23-29)
Measure: Plasma methylation biomarker: PARP1 methylation in plasma cell-free DNA
Time: At baseline, a day before surgery and 90 days after surgery
Measure: Plasma methylation biomarker: BRCA1,2 methylation in plasma cell-free DNA
Time: At baseline, a day before surgery and 90 days after surgery
Measure: Plasma methylation biomarker: ERCC1 methylation in plasma cell-free DNA
Time: At baseline, a day before surgery and 90 days after surgery
Measure: Plasma methylation biomarker: RAD51C methylation in plasma cell-free DNA
Time: At baseline, a day before surgery and 90 days after surgery
Measure: Single-nucleotide polymorphisms: PARP-1 Val762Ala
Time: Sample will be collected once at baseline
Measure: Single-nucleotide polymorphisms: ERCC1 Asn118Asn (C/T)
Time: Sample will be collected once at baseline
Measure: Single-nucleotide polymorphisms:ERCC2 Lys751Gln (T/G)
Time: Sample will be collected once at baseline
Measure: Single-nucleotide polymorphisms: GSTP1 Ile105Val (A/G)
Time: Sample will be collected once at baseline
Measure: Single-nucleotide polymorphisms: XPD Lys751Gln (A/C, C/C)
Time: Sample will be collected once at baseline
Measure: Single-nucleotide polymorphisms: XRCC1 Arg399Gln (G/A)
Time: Sample will be collected once at baseline
Measure: Circulating tumor cells (CTCs) evaluated for DNA repair biomarkers
Time: At baseline, a day before surgery and 90 days after surgery
Measure: Circulating tumor cells (CTCs) evaluated for PD-L1
Time: At baseline, a day before surgery and 90 days after surgery
Purpose: Treatment
Allocation: Randomized
Factorial Assignment
There are 4 SNPs
SNPs
1 I105V
Single-nucleotide polymorphisms: GSTP1 Ile105Val (A/G). --- Ile105Val ---
2 K751Q
Single-nucleotide polymorphisms:ERCC2 Lys751Gln (T/G). --- Lys751Gln ---
Single-nucleotide polymorphisms: XPD Lys751Gln (A/C, C/C). --- Lys751Gln ---
3 R399Q
Single-nucleotide polymorphisms: XRCC1 Arg399Gln (G/A). --- Arg399Gln ---
4 V762A
Single-nucleotide polymorphisms: PARP-1 Val762Ala. --- Val762Ala ---
HPO Nodes
HPO:Carcinoma
Genes 16
POLE MSH2 DKC1 SMARCA4 NLRP1 POLD1 CDKN1B MLH1 RSPO1 FGFR3 BCL10 APC STK11 PTEN APC KIT hr>Squamous cell carcinoma
Genes 79
COL7A1 WNT10A CDKN2A GJB6 FDPS LZTS1 GTF2H5 TERT NLRP1 ERCC5 NUTM1 ERCC2 RSPO1 LAMA3 TMC8 CTSC ING1 RECQL4 GJB2 ERCC2 TGFBR2 ERCC4 LAMC2 LAMB3 MPLKIP TARS1 ERCC3 XPC DOCK8 BLM NTHL1 TYR PSENEN WRAP53 GTF2E2 IL7 RNF6 SLC17A9 TNFRSF10B DKC1 POLH RECQL4 BLM BRD4 KRT5 TMC6 TERC ERCC2 SASH1 WNT10A MC1R CIB1 SLC45A2 MVD WRN KRT14 DDB2 RNF113A DCC FERMT1 TYR COL7A1 ERCC3 ERCC3 COL7A1 MMP1 COL7A1 GJB2 SLX4 MMP1 LMNA MVK TINF2 WWOX GJB2 OCA2 CIB1 POLH STAT1 hr>