| Eligibility |
Inclusion Criteria:
1. Histology: patients with soft-tissue sarcoma histologically confirmed by central
review (Pr Coindre team), except if the diagnosis was already confirmed by the RRePS
Network,
2. Upper/Lower limb or trunk wall soft-tissue sarcoma,
3. Age = 18 years,
4. Locally advanced or locally recurrent primitive tumor, outside any previously
irradiated field. Patients presenting operable locally Advanced or lacally recurrent
tumor can be included. Patients with metastases can be included.
5. Eastern Cooperative Oncology Group (ECOG) performance status = 2,
6. Life expectancy = 6 months,
7. At least one lesion, not previously irradiated, that can be accurately measured at
baseline as = 10 mm in the longest diameter (except lymph nodes which must have short
axis = 15 mm) with magnetic resonance imaging (MRI) and which is suitable for accurate
repeated measurements,
8. Adequate hematological, renal, metabolic and hepatic function:
- Haemoglobin = 9 g/dL and no blood transfusions in the 14 days prior to study
entry
- Absolute neutrophil count (ANc) = 1.5 x 109/L
- Platelets = 100 x 109/L
- Total bilirubin = 1.5 x upper limit of normality (ULN),
- Alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) = 2.5 x ULN,
- Serum creatinine = 150 µmol/L or creatinine clearance = 50 mL/min (according to
local institution) in case of serum creatinine > 150 µmol/L,
- TP, INR = 1.5 x ULN
9. Women of childbearing potential must have a negative serum pregnancy test within 28
days of study treatment, confirmed prior to treatment on day 1. Female patients of
child bearing 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 month after last dose of study
drug. Males patients, 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 3 month after last dose of study drug. Acceptable birth
control methods are described in appendix 10.
Subjects of non-childbearing potential are those who have:
- Amenorrheic for 1 year or more following cessation of exogenous hormonal
treatments,
- LH and FSH levels in the post menopausal range for women under 50,
- radiation-induced oophorectomy with last menses >1 year ago,
- chemotherapy-induced menopause with >1 year interval since last menses,
- or surgical sterilisation (bilateral oophorectomy or hysterectomy).
10. Patient is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up,
11. Voluntary signed and dated written informed consent prior to any specific procedure,
12. Patients with a social security in compliance with the Law.
Exclusion Criteria:
1. Any previous treatment with a PARP inhibitor, including Olaparib,
2. Patients unable to swallow orally administered medication and patients with
gastrointestinal disorders likely to interfere with absorption of the study
medication,
3. Immunocompromised patients, e.g., patients who are known to be serologically positive
for human immunodeficiency virus (HIV) and are receiving antiviral therapy,
4. Patients with known active hepatic disease (i.e., Hepatitis B or C) due to risk of
transmitting the infection through blood or other body fluids,
5. Patients considered a poor medical risk due to a serious, uncontrolled medical
disorder, non-malignant systemic disease or active, uncontrolled infection. Examples
include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3
months) myocardial infarction, unstable spinal cord compression (untreated and
unstable for at least 28 days prior to study entry), superior vena cava syndrome,
extensive bilateral lung disease on HRCT scan or any psychiatric disorder that
prohibits obtaining informed consent,
6. Patients with uncontrolled seizures,
7. Men or women of childbearing potential who are not using an effective method of
contraception as previously describes; women who are pregnant or breast feeding,
8. No prior or concurrent malignant disease diagnosed or treated in the last 2 years,
except for adequately treated in situ carcinoma of the cervix, basal or squamous skin
cell carcinoma, or in situ transitional bladder cell carcinoma,
9. Patients receiving any systemic chemotherapy within 2 weeks from the last dose prior
to study treatment (or a longer period depending on the defined characteristics of the
agents used),
10. Concomitant use of known CYP3A4 inhibitors such as ketokonazole, itraconazole,
ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir,
11. Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or
family history of long QT syndrome,
12. Blood transfusions within 14 days prior to study start,
13. Patients with myelodysplastic syndrome/acute myeloid leukaemia,
14. Major surgery within 14 days of starting study treatment and patients must have
recovered from any effects of any major surgery,
15. Participation to a study involving a medical or therapeutic intervention in the last
30 days,
16. Patient unable to follow and comply with the study procedures because of any
geographical, familial, social or psychological reasons,
17. Previous enrollment in the present study,
18. Patients with a known hypersensitivity to olaparib or any of the excipients of the
product.
19. Patients who not have recovered from any effects of any major surgery
20. Individuals deprived of liberty or placed Under legal guardianship
21. Patients who have tumor in contact with, invading or encasing for more than 50% any
major blood vessels
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