Supplementary file: Inclusion/exclusion criteria
Inclusion criteria
For inclusion in the study, subjects must fulfil all of the following criteria:
- Provision of written informed consent
- Male or female aged 18 years or older
- Histologically or cytologically confirmed metastatic cancer, not amenable to surgery or radiation therapy with curative intent
- Measurable or evaluable disease
- ECOG Performance status 0–2
- Estimated life expectancy of at least 12 weeks
- Negative pregnancy test for women of childbearing potential only (lack of childbearing potential is met by being post-menopausal, being surgically sterile, practising contraception with an oral contraceptive or other hormonal therapy [eg, hormone implants], intra-uterine device, diaphragm with spermicide or condom with spermicide, or being sexually inactive)
- Adequate bone marrow, hepatic and renal function defined as:
–Haemoglobin ≥10.0 g/dL
–WBC >3 x 109 L
–Absolute neutrophil count ≥1.5 x 109 L
–Platelets ≥100 x 109 L
–Total bilirubin ≤1.5 x upper limit of normal (ULN)
–Aspartate transaminase (AST)(SGOT) and alanine transaminase (ALT)(SGPT) ≤2.5 x ULN (or ≤5 x ULN in the presence of liver metastases)
–Serum creatinine ≤1.5 x ULN
- The patient is willing and able to comply with the protocol for the duration of the study period, including undergoing treatment and scheduled visits and examinations
Exclusion criteria
Any of the following is regarded as a criterion for exclusion from the study:
- More than three prior lines of chemotherapy for advanced disease
- Less than 28 days from active treatment (ie, any treatment used to treat the disease)
or high-dose radiotherapy (patients may continue concomitant use of stable dose of bisphosphonates if used at least 28 days prior to commencing study treatment and patients may receive palliative radiotherapy for bone disease during the study) - Prior treatment with >300 mg/m2 cumulative dose of doxorubicin equivalent
- Resistance to anthracyclines defined as progressive disease during anthracycline treatment or within 6 months after the last anthracycline administration
- Symptomatic or known central nervous system tumours or metastases
- Persistent CTC grade 2 or greater toxicities (excluding alopecia) caused by prior therapy
- 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, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, hepatic or renal disease, or any psychiatric disorder that prohibits obtaining informed consent
- Presence of gastrointestinal disorders that, in the investigator’s opinion, are likely to interfere with the absorption of olaparib or with the patient’s ability to take regular oral medication
- Patients known to be hypersensitive to liposomal doxorubicin, olaparib or any excipients of the products
- Patients with clinically significant cardiovascular disease or who have experienced clinically significant cardiovascular disease within the last 12 months
- Patients requiring treatment with potent inhibitors or inducers of CYP3A4
- Any concurrent condition which, in the investigator’s opinion, makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol
- Simultaneous participation in any other study involving an investigational medicinal product, or having participated in a study less than 28 days prior to the start of study treatment
- A positive pregnancy test. Pregnant or breast-feeding patient or patient of childbearing potential unless effective methods of contraception are used (lack of childbearing potential is met by being post-menopausal, being surgically sterile, practising contraception with an oral contraceptive or other hormonal therapy [eg, hormone implants], intra-uterine device, diaphragm with spermicide or condom with spermicide, or being sexually inactive). Patients and their partners must agree to use one of the above forms of contraception throughout the treatment period and for 6 months after discontinuation of treatment
- Patients who are unable to swallow orally administered medication
- Patients who are immune-compromised, eg, patients known to be serologically positive for human immunodeficiency virus (HIV)
- Left ventricular ejection fraction below 50%
- Major thoracic or abdominal surgery in 4 weeks prior to start of treatment
- Previous treatment with olaparib or other drug with similar mode of action