Histologically proven operable squamous cell carcinoma of the head and neck. MedDRA version: 18.1 Level: PT Classification code 10060121 Term: Squamous cell carcinoma of head and neck System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Lynparza
Pharmaceutical Form: Tablet
INN or Proposed INN: olaparib
CAS Number: 763113-22-0
Current Sponsor code: AZD2281, KU
Sponsors
Hellenic Cooperative Oncology Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Provision of signed written informed consent prior to any study specific procedures 2.Female and/or male patients aged 18 years and over 3.Newly diagnosed histologically proven squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx 4.Provision of biological material (tumor tissue and blood), provision of signed informed consent for translational research 5.Patients selected for a primary surgical treatment 6.No prior anti-cancer treatment for head and neck cancer 7.Performance status ECOG 0-1 8.Adequate hematological status: neutrophils (ANC) =1.5x109/L; platelets =100x109/L; haemoglobin =10g/dL 9.Adequate renal function: serum creatinine level 1.5 mg/dl and Glomelular Filtration Rate50 ml/min by Cockroft/Gault formula 10.Adequate liver function: serum bilirubin =1.5 x upper normal limit (ULN), alkaline phosphatase, AST, ALT 5xULN 11.No active rheumatoid arthritis, active inflammatory bowel disease, chronic infections, or any other disease or condition associated with chronic inflammation. 12.Ability to swallow tablets. 13.Regular follow-up feasible 14.Baseline evaluations performed before registration: clinical and blood evaluations no more than 1 week (7 days) prior to registration, tumour assessment (CT or MRI scan of the head and neck, chest, abdomen and pelvis at the discretion of the investigator) no more than 30 days prior to registration 15.Treatment initiation planned less than 1 week (7 days) after registration 16.For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior of starting study treatment 17.Women of childbearing potential and their partners, who are sexually active, must agree to the use of TWO highly effective forms of contraception in combination, throughout the period of taking study treatment and for at least 1-6 month (according to the treatment group) after last dose of study drug(s) (where applicable). Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of TWO highly effective forms of contraception in combination, throughout the period of taking study treatment and for 3-6 months (according tot he treatment group) after last dose of study drug(s) (where applicable). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: 1. Metastatic or locally advanced unresectable disease 2.Uncontrolled hypercalcemia 3.Concomitant unplanned antitumour therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy) 4.Treatment with any other investigational medicinal product within 28 days prior to study entry 5.Other serious and uncontrolled non-malignant chronic disease 6.Treatment with CYP3A4 inhibitors as well as inducers, unless discontinued 7 days prior to randomization 7.Any of the following within 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis 8.Other concomitant or previous malignancy, except: i) adequately treated in-situ carcinoma of the uterine cervix, ii) basal or squamous cell carcinoma of the skin, iii) cancer in complete remission for 5 years 9.Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days 10.Pregnant or breastfeeding women 11.Patients with known allergy to any excipients to study drugs 12.History of myocardial infarction and/or stroke or other arterial thrombotic events or pulmonary embolism or unstable angina pectoris within 6 months prior to registration 13.No features suggestive of MDS/ AML 14.Poorly controlled cardiac arrhythmias 15.Bowel obstruction 16.History of severe tumour bleeding or bleeding disorders 17.No blood transfusion within the 28 days prior to study 18.Poorly controlled anti-coagulation therapy (INR3.0 on coumadin or heparin compounds) 19.Palliative radiation therapy within 4 weeks prior to registration 20.Pregnancy or men or women of reproductive age not agreeing to use contraceptive measures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the difference in change in the tumour Ki-67 before and after treatment with the combination of olaparib + cisplatin or olaparib monotherapy. ; Secondary Objective: 1.To assess the objective response rate according to RECIST 1.1 criteria 2.To assess the pathologic complete response rate 3.To determine the metabolic response rate assessed by FDG-PET/CT scan (optional) 4.To assess the tolerability of treatment 5.To assess the surgical complication rate. 6.To identify potential biomarkers that could be used for correlation with response: a.Mutations in genes associated with DNA repair b.Expression of tissue biomarkers: PARP1, BRCA1,2, ERCC1. c.Plasma methylation biomarkers: PARP1, BRCA1,2, ERCC1, RAD51C methylation in plasma cell-free DNA d.Single-nucleotide polymorphisms: PARP-1 Val762Ala, ERCC1 Asn118Asn (C/T), ERCC2 Lys751Gln (T/G), GSTP1 Ile105Val (A/G), XPD Lys751Gln (A/C, C/C), XRCC1 Arg399Gln (G/A) e.Circulating tumor cells (CTCs) evaluated for DNA repair biomarkers and PD-L1 ;Primary end point(s): To investigate the difference in change in the tumour Ki-67 before and after treatment with the combination of olaparib + cisplatin and olaparib monotherapy;Timepoint(s) of evaluation of this end point: At baseline and at the day of the surgery or 2nd biopsy (at days 23-29 days). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.To assess the objective response rate according to RECIST 1.1 criteria 2.To assess the pathologic complete response rate 3.To determine the metabolic response rate assessed by FDG-PET/CT scan (optional) 4.To assess the tolerability of treatment 5.To assess the surgical complication rate. 6.To identify mutations in genes associated with DNA repair 7.To identify the expression of tissue biomarkers: PARP1, BRCA1,2, ERCC1. 8.To identify plasma methylation biomarkers: PARP1, BRCA1,2, ERCC1, RAD51C methylation in plasma cell-free DNA 9.To identify single-nucleotide polymorphisms: PARP-1 Val762Ala, ERCC1 Asn118Asn (C/T), ERCC2 Lys751Gln (T/G), GSTP1 Ile105Val (A/G), XPD Lys751Gln (A/C, C/C), XRCC1 Arg399Gln (G/A) 10.To identify circulating tumor cells (CTCs) evaluated for DNA repair biomarkers and PD-L1 ; Timepoint(s) of evaluation of this end point: 1. Imaging studies will be performed at baseline and on week 4. 2. On week 4 only for operable patients. 3. At baseline, on week 4. 4. Every week for all study duration and 30 days after last therapy administration. 5. Up to 30 days after surgery or the day of initiation of the next anticancer therapy. 6. At baseline, on day of surgery or the 2nd biopsy (at days 23-29) 7. At baseline, on day of surgery or the 2nd biopsy (at days 23-29) 8. At baseline, a day before surgery and 30 days after surgery. 9. Sample will be collected once at baseline 10. At baseline, a day before surgery and 30 days after surgery. | — |
Countries
Greece
Contacts
Public ContactClincal Trials
Hellenic Cooperative Oncology Group
Outcome results
None listed