Olaparib and Radiotherapy in Head and Neck Cancer
Klíčová slova
Abstraktní
Termíny
| Poslední ověření: | 03/31/2020 |
| První předloženo: | 08/27/2014 |
| Odhadovaná registrace vložena: | 08/27/2014 |
| První zveřejnění: | 08/31/2014 |
| Poslední aktualizace byla odeslána: | 04/14/2020 |
| Poslední aktualizace zveřejněna: | 04/16/2020 |
| Aktuální datum zahájení studie: | 09/23/2014 |
| Odhadované datum dokončení primární: | 01/13/2020 |
| Odhadované datum dokončení studie: | 03/31/2021 |
Stav nebo nemoc
Intervence / léčba
Radiation: radiotherapy and olaparib
Drug: radiotherapy and olaparib
Fáze
Skupiny zbraní
| Paže | Intervence / léčba |
|---|---|
| Experimental: radiotherapy and olaparib Radiotherapy will be given with accelerated fractionation following the DAHANCA schedule Olaparib: dose escalation | Radiation: radiotherapy and olaparib Primary tumor and lymph nodes will receive 35 fractions of 2 Gy resulting in a total dose of 70 Gy. Elective fields will receive 35 fractions of 1.55 Gy resulting in a total dose of 54.25 Gy in case a SIB technique is used, or 23 fractions of 2 Gy resulting in a total dose of 46 Gy in case a sequential boost technique is used. The higher total prescribed physical dose to the elective fields in a SIB technique based RT plan compensates for the lower dose per fraction and results in an equal biological effective dose when compared with a sequential boost technique. |
Kritéria způsobilosti
| Věky způsobilé ke studiu | 18 Years Na 18 Years |
| Pohlaví způsobilá ke studiu | All |
| Přijímá zdravé dobrovolníky | Ano |
| Kritéria | Inclusion Criteria: - ≥18 years of age - Histologically confirmed squamous cell carcinoma of the larynx stage II-III (T2N0M0 or T1-2N1M0 or T3N0-1M0) or histologically confirmed squamous cell carcinoma of the oropharynx stage II-III (T1-2N1M0 or T3N0-1M0) - In case of oropharyngeal carcinoma: tumor HPV status negative - WHO performance 0-1 - Life expectancy of at least 6 months - Adequate hematological, renal and hepatic functions - Hemoglobin ≥ 6.2 mmol/l - Leucocytes 3.0 x 10E9/l - Absolute neutrophil count 1.5x10E9/l - Platelet count 100 x 10E9/l - Total bilirubin ≤ 1.5 x UNL - ASAT/ALAT ≤ 2.5 x UNL - Creatinine clearance 50 ml/min; measured using a 24-hours urine sample or calculated using the Cockcroft-Gault formula - 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) - Patients of reproductive potential must agree to practice two effective medically approved contraceptive method during the trial and 3 months afterwards - Signed written informed consent. Exclusion Criteria: - Patients eligible for concurrent chemoradiotherapy rather than radiotherapy alone - 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) - 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. - Major surgery within two weeks of starting study treatment. - Participation in other trial with investigational drug or treatment modality - Gastrointestinal disorders that may interfere with absorption of the study drug or patients who are not able to take oral medication. - Tube feeding before the start of treatment. - Prior radiotherapy to head & neck region. - Blood transfusion in the four weeks prior to study entry - Persistent toxicities (CTC ≥ grade 2) with the exception of alopecia, caused by previous cancer therapy - QT-interval >470 msec - Significant cardiovascular disease as defined by: - History of congestive heart failure defined as NYHA class III - History of unstable angina pectoris or myocardial infarction up to 3 months prior to trial entry; - Presence of severe valvular heart disease - Presence of a ventricular arrhythmia requiring treatment; - Uncontrolled hypertension - Patients considered a poor medical risk due to: - non-malignant systemic disease - active, uncontrolled infection requiring parenteral antibiotics - a serious, uncontrolled medical disorder; examples include, but are not limited to: - uncontrolled major seizure disorder - unstable spinal cord compression - superior vena cava syndrome - extensive bilateral lung disease on HRCT scan - any psychiatric disorder that prohibits obtaining informed consent. - Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. - Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy. - Patients with known active hepatic disease (i.e. Hepatitis B or C) - Patients with myelodysplastic syndrome/acute myeloid leukaemia or features suggestive of MDS/AML on peripheral blood smear. - Concomitant medications: - Any previous treatment with a PARP inhibitor, including olaparib - 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 - Breast-feeding women |
Výsledek
Primární výsledná opatření
1. The incidence of dose limiting toxicities [1 year]
Měření sekundárních výsledků
1. acute toxicity [until 3 months after treatment]
2. late toxicity [3 months until 2 year after treatment]
