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Report for Clinical Trial NCT02882308

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Phase II(Window) Preoperative Study of Olaparib With Cisplatin or With Durvalumab (MEDI4736) or Alone or no Treatment in Patients With Histologically Proven Squamous Cell Carcinoma of the Head and Neck Who Are Candidates for Surgery.

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.

NCT02882308 Squamous Cell Carcinoma of the Head and Neck
MeSH:Carcinoma Carcinoma, Squamous Cell Squamous Ce Squamous Cell Carcinoma of Head and Neck
HPO:Carcinoma Squamous cell carcinoma

4 Interventions

Name: Olaparib

Description: 50/25 mg BD split x 5 days
Type: Drug
Group Labels: 1

Combination of cisplatin and olaparib

Name: Cisplatin

Description: 60 mg/m^2 d1-d5
Type: Drug
Group Labels: 1

Combination of cisplatin and olaparib

Name: Olaparib

Description: 300 mg BD x 21-28 days.
Type: Drug
Group Labels: 2

Combination of durvalumab and olaparib Monotherapy with olaparib

Name: Durvalumab

Description: 1500 mg d1
Type: Drug
Group Labels: 1

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: