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Guadecitabine and Carboplatin in Treating Patients with Extensive Stage Small Cell Lung Cancer

Trial Status: Active

This phase II trial studies how well guadecitabine and carboplatin work in treating patients with small cell lung cancer that has spread outside of the lung in which it began or to other parts of the body (extensive stage). Guadecitabine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving guadecitabine and carboplatin may work better in treating patients with extensive stage small cell lung cancer compared to other standard of care chemotherapy drugs.

Inclusion Criteria

  • Histological or cytological diagnosis of extensive-stage small cell lung cancer. 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
  • Patients must have received first line therapy with a platinum-based chemotherapy. Patients should not have received more than 1 prior line of chemotherapy (could have received immunotherapy which does not count as chemotherapy)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
  • Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) version(v)1.1. Subjects may have bone-only disease. * NOTE: Bone-only subjects are eligible if their disease can be documented/evaluated by bone scans, computed tomography (CT) or magnetic resonance imaging (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
  • Hemoglobin >= 9.0 g/dL
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Total bilirubin =< 1.5 x upper limit of normal (ULN). For subjects with Gilbert’s disease, total bilirubin =< 3 x ULN
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN. For subjects with documented liver metastases, ALT and AST =< 5 x ULN
  • Estimated glomerular filtration rate (eGFR) >= 60 mL/minute/1.73 m^2 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 a double-barrier method of birth control from the screening visit through 3 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 human immunodeficiency virus [HIV]/acquired immunodeficiency syndrome [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

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: ACTIVE
Contact: Shadia Ibrahim Jalal
Phone: 317-274-3589
Richard L. Roudebush Veterans Affairs Medical Center
Status: ACTIVE
Contact: Jordan Marie Schmitt
Muncie
IU Health Ball Memorial Hospital
Status: ACTIVE
Contact: Cathleen Carlos
Phone: 765-751-5850

PRIMARY OBJECTIVES:

I. Determine progression free survival (PFS) of the combination of guadecitabine and platinum in patients with extensive stage small cell lung cancer previously treated with platinum containing chemotherapy.

SECONDARY OBJECTIVES:

I. Evaluate the toxicity profile of the combination of guadecitabine and carboplatin in patients with extensive stage small cell lung cancer patients previously treated with platinum containing chemotherapy.

II. Estimate objective response rate (ORR) of the combination of guadecitabine and carboplatin in the above mentioned population.

III. Estimate disease control rate of the combination of guadecitabine and carboplatin in the above mentioned population.

IV. Estimate overall survival (OS) of the combination of guadecitabine and carboplatin in the above mentioned population.

CORRELATIVE/EXPLORATORY OBJECTIVES:

I. Measure platinum induced deoxyribonucleic acid (DNA) adducts in peripheral blood mononuclear cells (PBMCs) and tumor tissue on cycle 1 day 1 and cycle 2 day 5 prior to carboplatin treatment.

II. Methylation status change in PBMCs and tumor biopsy for global DNA and selected genes in tumor tissue on cycle 1 day 1 and cycle 2 day 5 prior to carboplatin treatment.

III. Analyze immunohistochemistry (IHC) expression of EZH2 and EZH2 target genes on cycle 1 day 1, cycle 2 day 5 prior to carboplatin treatment and at progression (optional).

IV. Determine circulating tumor cell (CTC) burden prior to initiating treatment.

OUTLINE:

Patients receive guadecitabine subcutaneously (SC) on days 1-5 and carboplatin intravenously (IV) over 15-30 minutes on day 5. Treatment repeats every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 2 months until disease progression, and then every 3 months until 1 year from time of documented disease progression.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Indiana University / Melvin and Bren Simon Cancer Center

Principal Investigator
Shadia Ibrahim Jalal

  • Primary ID LUN17-302
  • Secondary IDs NCI-2019-02949
  • Clinicaltrials.gov ID NCT03913455