SNPMiner Trials: Clinical Trial Report
Report for Clinical Trial NCT02882308
Developed by Shray Alag, 2019.
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
Monotherapy with olaparib Combination of durvalumab and 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 11
PTEN CDKN1B APC MLH1 MSH2 FGFR3 KIT DKC1 RSPO1 STK11 NLRP1 hr>Squamous cell carcinoma
Genes 62
BLM TYR CDKN2A NUTM1 TGFBR2 KRT5 COL7A1 GTF2E2 GJB2 ERCC2 KRT14 ERCC3 CIB1 ERCC4 ERCC5 WWOX LMNA SASH1 RNF6 TINF2 ING1 SLC17A9 DOCK8 LZTS1 PSENEN FDPS NTHL1 CTSC GJB6 BRD4 POLH RECQL4 RNF113A TMC6 FERMT1 MC1R WRN TMC8 LAMA3 MPLKIP GTF2H5 WNT10A DKC1 LAMB3 NLRP1 LAMC2 SLC45A2 OCA2 XPC MMP1 TNFRSF10B DCC WRAP53 TERC TERT RSPO1 DDB2 SLX4 STAT1 MVD IL7 MVK hr>