Olaparib and Radiotherapy in Head and Neck Cancer

Launched by THE NETHERLANDS CANCER INSTITUTE · Aug 28, 2014

Keywords

ClinConnect Summary

This clinical trial is studying the combination of a medication called olaparib and radiation therapy for patients with stage II-III laryngeal cancer or HPV-negative oropharyngeal cancer. The goal is to see if adding olaparib, which can help make cancer cells more sensitive to radiation, will improve treatment outcomes without increasing side effects. Previous research suggests that olaparib might enhance the effectiveness of radiation by preventing cancer cells from repairing the damage done by the treatment.

To participate in this trial, patients need to be at least 18 years old and have a confirmed diagnosis of stage II-III squamous cell carcinoma of the larynx or oropharynx. They should also be in good overall health, with specific lab results that show their blood and organ functions are within acceptable ranges. Participants will receive radiation therapy along with olaparib and will be monitored closely for any side effects or reactions. It's important for potential participants to discuss this opportunity with their doctors to determine if they meet all eligibility criteria and to understand the commitment involved in being part of the trial.

Gender

ALL

Eligibility criteria

• 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