Olaparib and Temozolomide in Treating Patients with Recurrent Small Cell Lung Cancer

Inclusion Criteria

• Participant must have histologically or cytologically confirmed small cell lung cancer and may not be a candidate for potentially curative therapy
• Presence of measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1): 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
• The small cell lung cancer must have progressed radiographically following a platinum-based (cisplatin and/or carboplatin) standard prior chemotherapy regimen; any number of interval prior lines of therapy is allowed; patients who have received prior platinum-based chemotherapy and radiation for limited stage SCLC and have subsequently developed relapsed disease are eligible, as long as the platinum-based therapy was given within 12 months prior to the time of relapse
• Hemoglobin >= 10.0 g/dL and no known active bleeding (within 28 days prior to administration of study treatment)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 28 days prior to administration of study treatment)
• White blood cells (WBC) > 3 x 10^9/L (within 28 days prior to administration of study treatment)
• Platelet count >= 100 x 10^9/L (within 28 days prior to administration of study treatment)
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (unless liver metastases are present in which case it must be =< 5 x ULN) (within 28 days prior to administration of study treatment)
• Serum creatinine =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to administration of study treatment)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Participant must have a life expectancy >= 16 weeks
• Women of childbearing potential must have a negative urine or serum pregnancy test within 28 days of initial dose of olaparib and temozolomide AND must agree to the use of two highly effective forms of contraception throughout their participation in the study and for at least 3 months after the last dose of olaparib and temozolomide, OR confirmed prior to treatment on day 1 to be postmenopausal or surgically sterile; postmenopausal is defined as: * Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments * Luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in the postmenopausal 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 sterilization (bilateral oophorectomy or hysterectomy)
• Participant is willing to comply with the protocol for the duration of the study, and undergo treatment and scheduled visits and examinations including follow up
• Participant must obtain prior approval from insurance to reimburse for oral temozolomide for the duration of the study or agree to self-pay for oral temozolomide

Exclusion Criteria

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous enrollment in the present study
• Participation in another clinical study with an investigational product during the 21 days prior to first dose of olaparib and temozolomide
• Participants 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 for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with olaparib and temozolomide
• Participants are to discontinue the use of the following classes of inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4); patients who are on these drugs are eligible if a washout period of a minimum of 7 days occurs before start of olaparib and temozolomide: * Azole antifungals * Macrolide antibiotics * Protease inhibitors
• Persistent clinically significant toxicities (>= CTCAE version [v.] 4.0 grade 2) caused by previous cancer therapy, with the exception of alopecia
• Participants with a previously documented diagnosis of myelodysplastic syndrome (MDS) (or any dysplastic leukocyte morphology suggestive of MDS) or acute myeloid leukemia
• Participants with symptomatic uncontrolled brain metastases; baseline brain imaging by CT or MRI is required for all patients; participants with brain metastases that have been treated with prior radiation therapy and are stable on a subsequent scan are allowed; participants with untreated possible brain metastases that are new at the time of screening and are < 1 cm and asymptomatic are allowed; the participant can receive corticosteroids as long as these were started and at a stable dose at least 28 days prior to treatment
• Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of any major surgery
• Participants 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, corrected QT interval (QTc) prolongation > 470 msec, 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), extensive bilateral lung disease with less than 20% predicted lung function by carbon monoxide diffusing capability test (DLCO) (lung diffusion capacity testing), or any psychiatric disorder that prohibits obtaining informed consent
• Participants unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
• Pregnant or breast feeding women; all patients (male and female) must agree to practice a medically acceptable method of contraception; should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately
• Patients who have a history of and are known to be serologically positive for human immunodeficiency virus (HIV) and are receiving antiviral therapy; baseline testing is not required
• Patients with known active hepatitis B or C; baseline testing is not required
• Patients with a known hypersensitivity to olaparib, temozolomide or any of the excipients of the products
• Patients with uncontrolled seizures
• Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumors curatively treated with no evidence of disease for >= 5 years
• Patients with current and symptomatic pneumonitis, or extensive bilateral lung disease on high resolution CT scan
• Patients with whole blood transfusion in the last 120 days prior to entry to the study
• Patients with previous allogeneic bone marrow transplant
• Patients with active, uncontrolled infection
• Patients who need to continue treatment with any prohibited medications
• Patients who have not completed the appropriate washout period for the prohibited medications