Head and Neck Cancer squamous cell cancer of Head and Neck
Conditions
Interventions
Radiotherapy (standard treatment): Radiotherapy will be given with conventional
fractionation schedule, Five fractions per week will be given. Overall
radiotherapy treatment time will be 7 weeks. Ac
Sponsors
Nederlands Kanker Instituut
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. >=18 years of age 2. Histologically confirmed squamous cell carcinoma of the larynx (T2N0M0 or T1-2N1-2bM0 or T3N0-2bM0 or patients with locally advanced disease who will not receive concurrent chemotherapy) or histologically confirmed squamous cell carcinoma of the oropharynx (T1-2N1-2bM0 or T3N0-2bM0 or patients with locally advanced disease who will not receive concurrent chemotherapy) 3. In case of oropharyngeal carcinoma: tumor HPV status negative, or history of smoking >= 10 pack years 4. WHO performance 0-1 5. Life expectancy of at least 6 months 6. Adequate hematological, renal and hepatic functions a. Hemoglobin >= 6.2 mmol/L b. Leucocytes >= 3.0 x 10E9/L c. Absolute neutrophil count >= 1.5x10E9/L d. Platelet count >= 100 x 10E9/L e. Total bilirubin = 50 ml/min; measured using a 24-hours urine sample or calculated using the Cockcroft-Gault formula 7. Evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 21 days of study treatment. Non-childbearing potential or postmenopausal is defined as: • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments • LH and FSH levels in post menopausal range for women under 50 years of age • Radiation-induced oophorectomy with last menses > 1 year ago • Chemotherapy-induced menopause with > 1 year interval since last menses • Surgical sterilisation (bilateral oophorectomy or hysterectomy) 8. Patients of reproductive potential must agree to practice two effective medically approved contraceptive method during the trial and 3 months afterwards 9. Signed written informed consent.
Exclusion criteria
Exclusion criteria: 1. Concurrent active malignancy other than localized, non-melanoma skin cancer or carcinoma-in-situ of the cervix (unless definitive treatment was completed 3 years or more before study entry and the patient has remained disease free) 2. Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 3 weeks prior to start of therapy (or a longer period depending on the defined characteristics of the agents used e.g. 6 weeks for mitomycin or nitrosourea). Patients may continue the use of LHRH agonists for cancer; bisphosphonates for bone disease and corticosteroids. 3. Major surgery within two weeks of starting study treatment. 4. Participation in other trial with investigational drug or treatment modality 5. Gastrointestinal disorders that may interfere with absorption of the study drug or patients who are not able to take oral medication. 6. Tube feeding before the start of treatment. 7. Prior radiotherapy to head & neck region. 8. Blood transfusion in the four weeks prior to study entry 9. Persistent toxicities (CTC >= grade 2) with the exception of alopecia, caused by previous cancer therapy 10. QT-interval >470 msec 11. Significant cardiovascular disease as defined by: a. History of congestive heart failure defined as NYHA class III b. History of unstable angina pectoris or myocardial infarction up to 3 months prior to trial entry; c. Presence of severe valvular heart disease d. Presence of a ventricular arrhythmia requiring treatment; e. Uncontrolled hypertension 12. Patients considered a poor medical risk due to: a. non-malignant systemic disease b. active, uncontrolled infection requiring parenteral antibiotics c. a serious, uncontrolled medical disorder; examples include, but are not limited to: i. uncontrolled major seizure disorder ii. unstable spinal cord compression iii. superior vena cava syndrome iv. extensive bilateral lung disease on HRCT scan v. any psychiatric disorder that prohibits obtaining informed consent. 13. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. 14. Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy. 15. Patients with known active hepatic disease (i.e. Hepatitis B or C) 16. Patients with myelodysplastic syndrome/acute myeloid leukaemia or features suggestive of MDS/AML on peripheral blood smear. 17. Concomitant medications: a. Any previous treatment with a PARP inhibitor, including olaparib b. Patients receiving the following classes of inhibitors of CYP3A4 (see paragraph 6.4.2 for guidelines and wash out periods) - Azole antifungals - Macrolide antibiotics - Protease inhibitors 18. Breast-feeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of dose limiting toxicities | — |
Secondary
| Measure | Time frame |
|---|---|
| 1)Toxicity and safety variables - Acute toxicity: severity, duration and relation with treatment of all adverse events according to CTCAE version 4.03 occurring from start of treatment until 3 months after end of treatment - Late toxicity: severity, duration and relation with treatment of possibly, probably or definitely related adverse events according to CTCAE version 4.03 occurring from 3 months after end of treatment until 2 years after end of treatment - Swallowing function preservation at 1 year - Tube feeding dependency at 1 year 2) PK variables of olaparib (steady state AUC, steady state C-max, steady state C-min) 3) Pd variables (PARP inhibition in PBMCs) 4) Variables assessing efficacy of the study treatment: - Objective response rate at 12 weeks after end of treatment - Locoregional control defined as absence of (pathologically confirmed) residual or recurrent tumor at primary site and in regional lymph node areas - Localisation of recurrences in relation to the planned radiotherapy fields: (boost) PTV - Progression free survival at two years after end of treatment | — |
Countries
Netherlands
Outcome results
None listed