| Eligibility |
Inclusion Criteria:
1. Provision of fully informed consent prior to any study specific procedures.
2. Subjects must be =20 years of age.
3. Small cell lung cancer(SCLC) that has progressed during or after first-line therapy.
- The 1st line regimen must have contained platinum based regimen.
- Refractory to first-line chemotherapy or relapse within 6 months since the last
dose of first-line chemotherapy
- If the patient correspond to sensitive relapse (relapse more than 6 months since
the last dose of first-line chemotherapy), she/he should get second-line
treatment.
4. Provision of tumor sample (from either archival or fresh biopsy)
5. Subjects are 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.
6. ECOG performance status of 0-2
7. Subjects must have a life expectancy = 3 months from proposed first dose date.
8. Subjects must have acceptable bone marrow, liver and renal function measured within
28days prior to administration of study treatment as defined below:
- Haemoglobin =10.0 g/dL with no blood transfusion the past 28days.
- Absolute neutrophil count (ANC) = 1.5 x 109/L
- White blood cells (WBC) = 3 x 109/L
- Platelet count =100 x 109/L
- Total bilirubin = 1.5 x institutional upper limit of normal (ULN) except for
subject with liver metastases for whom total bilirubin is = 3 x ULN
- AST(SGOT)/ALT(SGPT) = 2.5 x institutional upper limit of normal(ULN) except for
subject with liver metastases for whom AST(SGOT)/ALT(SGPT) is = 5x ULN
- Alkaline phosphatase(ALP) = 2.5 x institutional upper limit of normal(ULN) except
for subject with liver metastases for whom ALP is = 5 x ULN. ALP is not
exclusionary if due to the presence of bone metastasis and liver function is
otherwise considered adequate in the investigator's judgement.
- Subjects must have creatinine clearance estimated using the Cockcroft-Gault
equation of =51 mL/min:
Estimated creatinine clearance = (140-age [years]) x weight (kg) x Fa serum creatinine
(mg/dL) x 72 a where F=0.85 for females and F=1 for males.
- Albumin = 33g/L
9. At least one measurable lesion that can be accurately assessed by imaging or physical
examination.
10. Evidence of non-childbearing status for women of childbearing potential: A woman of
childbearing potential must have a negative or urine pregnancy test at screening and
confirmed prior to treatment on Cycle 1 Day 1
11. Female subjects who are not of childbearing potential and fertile female subjects of
childbearing potential who agree to use adequate contraceptive measures, who are not
breastfeeding. For women, must agree to use a barrier method of birth control. must
agree to use a barrier method of birth control for 3months after treatment stops.
12. Fertile male patients willing to use at least one medically acceptable form of birth
control, and must not donate sperm, for the duration of the study, and for 6months
after treatment stops.
13. Provision of informed consent for genetic research. If a patient declines to
participate in the genetic research, there will be no penalty or loss of benefit to
the patient. The patient will not be excluded from other aspects of the study
described in this Clinical Study Protocol, so long as they consent to that part.
Exclusion Criteria:
1. Previous enrolment in the present study
2. More than two prior chemotherapy regimen for the treatment of small cell lung cancer
3. Any previous treatment with ATR inhibitor and PARP inhibitor, including olaparib
4. Patients with second primary cancer, except: adequately treated non-melanoma skin
cancer, curatively treated in-situ cancer of the cervix, or other solid tumours
curatively treated with no evidence of disease for >2 years.
5. Subjects unable to swallow orally administered medication.
6. Treatment with any investigational product during the last 14 days before the
enrollment (or a longer period depending on the defined characteristics of the agents
used).
7. Subjects receiving any systemic chemotherapy, radiotherapy (except for palliative
reasons), within 2 weeks from the last dose prior to study treatment The patient can
receive a stable dose of bisphosphonates or denosumab for bone metastases, before and
during the study as long as these were started at least 4 weeks prior to treatment.
8. Concomitant use of known sensitive CYP3A4 substrates or CYP3A4 substrates with a
narrow therapeutic index, or to be moderate to strong CYP3A4 inhibitor/inducer which
cannot be discontinued to 2weeks prior to Day 1 of dosing(except for St. John's Wort,
which is 3 weeks) and withheld throughout the study until 4weeks after the last dose
of study drug, Co-administration of aprepitant or fosaprepitant or Pgp
inhibitor/inducer during this study is prohibited Refer to the Section 8.3.2 and
Appendix H for listing of all prohibited medications.
9. With the exception of alopecia, any ongoing toxicities (>CTCAE 4.03 grade 1) caused by
previous cancer therapy.
10. Intestinal obstruction or CTCAE 4.03 grade 3 or grade 4 upper GI bleeding within
4weeks before the enrollment.
11. Subjects with myelodysplastic syndrome/acute myeloid leukemia or with features
suggestive of MDS/AML.
12. Resting ECG with measurable QTc > 470 msec on 3 or more time points within a 24 hour
period or any factors that increase the risk of QTc prolongation or risk of arrhythmic
events such as heart failure, hypokalaemia, congenital long QT syndrome, immediate
family history of long QT syndrome or unexplained sudden death under 40 years of age.
13. Subjects with cardiac problem as follows: unstable angina pectoris, congestive heart
failure, acute myocardial infarction, conduction abnormality not controlled with
pacemaker or medication, significant ventricular or supraventricular arrhythmias
(patients with chronic rate controlled atrial fibrillation in the absence of other
cardiac abnormalities are eligible).
14. Subjects at risk of brain perfusion problems(e.g., carotid stenosis hypotension,
including a fall in blood pressure of >20mm Hg)
15. Subjects with relative hypotension (< 100/60 mm Hg) or clinically relevant orthostatic
16. Uncontrolled hypertension requiring clinical intervention.
17. Female patients who are breast-feeding or child-bearing
18. Any evidence of severe or uncontrolled systemic disease, active infection, active
bleeding diatheses or renal transplant, including any subjects known to have human
immunodeficiency virus (HIV), active hepatitis B or active hepatitis C
19. Major surgical procedures =28 days of beginning study treatment, or minor surgical
procedures =7 days
20. Known central nervous system (CNS) disease other than neurologically stable,treated
brain metastases - defined as metastasis having no evidence of progression or
haemorrhage for at least 2weeks after treatment.
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