Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer

Phase 2

Completed

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

Interventions: Drug: Guadecitabine
Drug: Carboplatin

Registration Number: NCT03913455

Lead Sponsor: Shadia Jalal, MD

Brief 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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 24

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Guadecitabine and Carboplatin	Carboplatin	Each cycle = 28 days; Subjects receive 4 cycles
Guadecitabine and Carboplatin	Guadecitabine	Each cycle = 28 days; Subjects receive 4 cycles

Primary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	Time of treatment start until the criteria for disease progression or death. Up to a maximum of 7 months.	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to a maximum of 7 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1
Disease Control Rate (DCR)	Up to a maximum of 7 months	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. DCR defined as CR + PR + Stable Disease (SD) \>=8 weeks per RECIST 1.1
Adverse Events	AEs had been recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 5 months	All adverse events (AEs) had been determined according to the NCI Common Terminology Criteria for (NCI CTCAE) V5. A summary of the total number of participants is provided.
Overall Survival (OS)	Time of treatment start until death or date of last contact, up to a maximum of 16 months.	Overall survival is defined as the time from treatment start until death or date of last contact.

Trial Locations

Locations (4): University of Virginia Health System
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Charlottesville, Virginia, United States
Indiana Univeristy Melvin and Bren Simon Cancer Center
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Indianapolis, Indiana, United States
IU Health Ball Memorial Cancer Center
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Muncie, Indiana, United States
University of Wisconsin, Clinical Cancer Center
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Milwaukee, Wisconsin, United States