Phase II, single-arm study of olaparib monotherapy in relapsed small cell lung cancer patients with HR pathway gene mutations not limited to BRCA 1/2 mutations, ATM deficiency or MRE11A mutations

Not Applicable

Recruiting

Conditions: Neoplasms

Registration Number: KCT0002276

Lead Sponsor: Samsung Medical Center

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 28

Inclusion Criteria

1. Provision of informed consent prior to any study specific procedures
2. Small cell lung cancer that satisfies one or more of the following conditions:
1) BRCA1 or BRCA2 mutation, ATM deficiency, MRE11A mutation
2) Mutation of other HR(homologous recombination) pathway genes: BLM, NBN, RAD50, RAD52, RAD54L, RAD51, RAD51B, RAD51C, RAD51D, RECQL, RECQL4, RECQL5, RPA1, WRN etc.
3. Small cell lung cancer 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. Patients (male/female) must be > 20 years of age.
5. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study
treatment as defined below:
?- Haemoglobin = 10.0 g/dL
?- Absolute neutrophil count (ANC) = 1.5 x 109/L
No features suggestive of MDS/AML on peripheral blood smear
?- White blood cells (WBC) > 3x109/L
?- Platelet count = 100 x 109/L
?- Total bilirubin = 1.5 x institutional upper limit of normal (ULN)
?- AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present in which
case it must be = 5x ULN
- Serum creatinine = 1.5 x institutional upper limit of normal (ULN) or creatinine clearance (CrCl) =50 mL/min
(Cockcroft-gault method)
6. ECOG(Eastern Cooperative Oncology Group) performance status 0-1
7. Patients must have a life expectancy = 16 weeks
8. Evidence of non-childbearing status for women of childbearing potential:
negative urine or serum pregnancy test within 28 days of study treatment, confirmed prior to treatment on day 1
Postmenopausal is defined as:
?- 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).
9. 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.
10. 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 computed tomography (CT) or magnetic
resonance imaging (MRI) and which is suitable for accurate repeated measurements.
11. 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. Involvement in the planning and/or conduct of the study
(applies to both AstraZeneca staff and/or staff at the study site)
2. Previous enrolment in the present study
3. Participation in another clinical study with an investigational product during the last 2 weeks
(or a longer period depending on the defined characteristics of the agents used).
4. Any previous treatment with a PARP inhibitor, including olaparib.
5. More than two prior chemotherapy regimen for the treatment of small cell lung cancer. Pazopanib maintenance or immune checkpoint inhibitor (CTLA4, PD-1 or PD-L1 monoclonal antibody) is not considered as line of treatment.
6. 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
7.Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). 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 with study drug.
8.Concomitant use of known CYP3A4 inhibitors such as ketokonazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir
9. Persistent toxicities (>=CTCAE grade 2) with the exception of alopecia, caused by previous cancer therapy.
10. Resting ECG with QTc > 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
11. Patients with myelodysplastic syndrome/acute myeloid leukaemia
12. Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment.
13. Major surgery within 14 days of starting study treatment or patients not being recovered from any effects of any major surgery
14. 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.
15. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
16. Breast feeding women
17. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy.
18. 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.
19. Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
20. Patients with uncontrolled seizures.

Study & Design

Study Type: Interventional Study

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR) by RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
- Duration of response (DOR), Disease control rate (DCR) at 12 week, Overall survival (OS) and progression-free survival (PFS) calculated by Kaplan-Meier method