Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer
Condition: Small Cell Lung Cancer; Extensive-stage Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma
Intervention: Guadecitabine; Carboplatin
Intervention description: Guadecitabine 30 mg/m2 subcutaneously Days 1-5; Carboplatin AUC 4 IV Day 5
Intervention MeSH terms: Carboplatin; Guadecitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.