Olaparib dose escalation in combination with high dose radiotherapy to the breast and regional lymph nodes in patients with breast cancer

Completed

Conditions: breast cancer
metastatic breast cancer
10006291

Registration Number: NL-OMON44691

Lead Sponsor: ederlands Kanker Instituut

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 72

Inclusion Criteria

For group A and B
1. *18 years of age
2. Patients should fulfill all inclusion criteria for patients with the tumor present in the breast (listed under point 3) OR all inclusion criteria for postoperative patients (listed under point 4)
3. For patients with the tumor present in the breast:
a. Histological proven breast cancer or local recurrence of breast cancer which is inoperable or/and metastatic, including inflammatory breast cancer
b. Tumor in breast accessible for biopsy
4. For postoperative patients:
a. Histological proven BC
b. Mastectomy or lumpectomy that is radical or focal irradical after (re-) excision
c. High risk of locoregional recurrence defined as:
- cN2-3 & (y)pN1-3 & non-operated pre-chemo, or pre-operative in case no neoadjuvant chemotherapy is given, PET-positive or PA-proven lymph nodes;
- or as judged by both the principle investigator and the treating physician
5. WHO performance 0-2
6. Life expectancy of at least 6 months
7. 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 ULN
f. ASAT/ALAT * 2.5 x ULN ; or in the presence of liver metastases * 5 x ULN
g. Creatinine clearance * 50 ml/min; measured or calculated
8. 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)
9 Patients of reproductive potential must agree to practice two effective medically approved contraceptive method during the trial and 3 months afterwards
10. Signed written informed consent
For arm A only:
11a Indication for breast irradiation without the use of skin bolus
For arm B only:
11b Indication for breast irradiation with the use of skin bolus

Exclusion Criteria

1. Anti-cancer therapy including chemotherapy, radiotherapy, immunotherapy or use of other investigational agents within 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 ornitrosourea). Patient may continue the use of tamoxifen, aromatase inhibitor and LHRH agonists for cancer; bisphosphonates for bone disease and corticosteroids. The use of denosumab for bone disease is not allowed.
2. Major surgery within two weeks of starting study treatment.
3. Participation in other trial with investigational drug or treatment modality
4. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required.
5. Prior ipsilateral radiotherapy to the chest or breast.
6. Blood transfusion in the four weeks prior to study entry
7. Persistent toxicities (CTC * grade 2) with the exception of alopecia, caused by previous cancer therapy
8. QT-interval >470 msec
9. 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
10. 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.
11. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
12. Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
13. Patients with known active hepatic disease (i.e. Hepatitis B or C)
14. Patients with myelodysplastic syndrome/acute myeloid leukaemia or features suggestive of MDS/AML on peripheral blood smear.
15. Gastrointestinal disorders that may interfere with absorption of the study drug or patients who are not able to take oral medication
16. Concomitant medications:
a. Any previous treatment with a PARP inhibitor, including Olaparib
b. Patients receiving the following classes of inhibitors of CYP3A4 (see Section 7.4 for guidelines and wash out periods)
i. Azole antifungals
ii. Macrolide antibiotics
iii. Protease inhibitors
17. Pregnant or breast-feeding women
18. Breast feeding women