Olaparib dose escalation trial in patients treated with radiotherapy for laryngeal and oropharyngeal squamous cell carcinoma

Completed

Conditions: Head and Neck Cancer
squamous cell cancer of Head and Neck
10027655

Registration Number: NL-OMON43772

Lead Sponsor: ederlands Kanker Instituut

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 36

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 <= 1.5 x UNL
f. ASAT/ALAT <= 2.5 x UNL
g. Creatinine clearance >= 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

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