guadecitabine in combination with carboplatin in extensive stage small cell lung cancer

Conditions: Small Cell Lung Cancer; Extensive-stage Small Cell Lung Cancer

Summary: this is a phase ii, open-label, single arm, single-stage study. both, chemo-sensitive and chemo-resistant patients will be enrolled and treated with 4 cycles of combination of guadecitabine and carboplatin


Eligibility criteria:
inclusion criteria: * male or female subjects, age ≥ 18 years. * histological or cytological diagnosis of small cell lung cancer. subjects must have extensive-stage disease is defined as disease beyond the ipsilateral hemithorax, mediastinum and ipsilateral supraclavicular area and including malignant pleural or pericardial effusion or hematogenous metastases. * patient should not have received more than 1 prior line of chemotherapy (could have received immunotherapy which does not count as chemotherapy). * ecog ps 0-1 * measurable disease as per recist v1.1. subjects may have bone-only disease. note: bone-only subjects are eligible if their disease can be documented/evaluated by bone scans, ct or mri. their disease will be assessed using md anderson criteria. note: previously irradiated lesions are eligible as a target lesion only if there is documented progression of the lesion after irradiation. * adequate bone marrow, liver, and renal function, as assessed by the following laboratory requirements: * hemoglobin ≥ 9.0 g/dl * absolute neutrophil count (anc) ≥ 1,500/mm3 * platelet count ≥ 100,000/mm3 * total bilirubin ≤ 1.5 x upper limit of normal (uln). for subjects with gilbert's disease, total bilirubin ≤ 3 x uln * alt and ast ≤ 2.5 x uln. for subjects with documented liver metastases, alt and ast ≤ 5×uln * international normalized ratio (inr) ≤1.5, if not therapeutically anticoagulated. subjects who are being therapeutically anticoagulated may be included provided that the anticoagulation regimen is stable and closely monitored. * estimated glomerular filtration rate (egfr) ≥ 60 ml/minute/1.73 m2 as determined using the cockcroft-gault formula. * women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. * male and female subjects of child- bearing potential must agree to use an effective method of birth control from the screening visit through 6 months after the last dose of study drug. exclusion criteria: * platinum refractory disease defined as disease progression during first line platinum containing chemotherapy regimen. progression following platinum based therapy is allowed. * prior therapy with a hypomethylating agent. * previously untreated (non-irradiated), symptomatic brain metastases. no prior treatment is required for non-symptomatic brain metastases. previously treated symptomatic brain metastases are permitted. * unstable or clinically significant concurrent medical condition, psychiatric illness or social situation that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol. * clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy. (suppressive therapy for chronic infections allowed, for example: subjects with hiv/aids with adequate antiviral therapy to control viral load would be allowed. subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy.) * hypersensitivity to (imp) or components of the study treatment regimen. * treated with any investigational drug within 3 weeks of first dose of study treatment. * pregnant or breastfeeding. * second malignancy currently requiring active therapy except breast or prostate cancer stable on or responding to endocrine therapy.