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NCT03913455

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

Completed Phase 2 Results posted Last updated 20 December 2023
What this trial tests

Phase 2 trial testing Guadecitabine in Small Cell Lung Cancer in 24 participants. Completed in 2 February 2022.

Timeline
6 June 2019
Primary endpoint
14 April 2021
2 February 2022

Quick facts

Lead sponsorShadia Jalal, MD
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment24
Start date6 June 2019
Primary completion14 April 2021
Estimated completion2 February 2022
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Shadia Jalal, MD

Who can join

18 and older, any sex, with Small Cell Lung Cancer or Extensive-stage Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) Primary · 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.

GroupValue95% CI
Guadecitabine and Carboplatin (Platinum Sensitive)1.91.2 – 2.5
Guadecitabine and Carboplatin (Platinum Resistant)1.70.9 – 4.1
Adverse Events Secondary · 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.

GroupValue95% CI
Guadecitabine and Carboplatin24
Objective Response Rate (ORR) Secondary · 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

GroupValue95% CI
Guadecitabine and Carboplatin (Platinum Sensitive)7.10.2 – 33.9
Guadecitabine and Carboplatin (Platinum Resistant)0NA – NA
Disease Control Rate (DCR) Secondary · 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

GroupValue95% CI
Guadecitabine and Carboplatin (Platinum Sensitive)42.917.7 – 71.1
Guadecitabine and Carboplatin (Platinum Resistant)33.37.5 – 70.1
Overall Survival (OS) Secondary · 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.

GroupValue95% CI
Guadecitabine and Carboplatin (Platinum Sensitive)6.82.7 – 10
Guadecitabine and Carboplatin (Platinum Resistant)4.41.4 – 11.4

Adverse events — posted to ClinicalTrials.gov

Time frame: All-Cause Mortality was monitored up to a maximum of 16 months. Serious Adverse Events and Other (Not Including Serious) Adverse Events were monitored for up to 5 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Guadecitabine and Carboplatin
Serious: 6/24 (25%)
Deaths: 18/24

Serious adverse events (5 terms)

ReactionSystemGuadecitabine and Carbopla…
SEPSISInfections and infestations
BACK PAINMusculoskeletal and connective tissue disorders
DYSPNEARespiratory, thoracic and mediastinal disorders
FEBRILE NEUTROPENIABlood and lymphatic system disorders
LOWER GASTROINTESTINAL HEMORRHAGEGastrointestinal disorders
Other adverse events (90 terms — click to expand)

ReactionSystemGuadecitabine and Carbopla…
FATIGUEGeneral disorders
ANEMIABlood and lymphatic system disorders
NAUSEAGastrointestinal disorders
NEUTROPHIL COUNT DECREASEDInvestigations
CONSTIPATIONGastrointestinal disorders
DYSPNEARespiratory, thoracic and mediastinal disorders
PAINGeneral disorders
ANOREXIAMetabolism and nutrition disorders
HYPOCALCEMIAMetabolism and nutrition disorders
INJECTION SITE REACTIONGeneral disorders
VOMITINGGastrointestinal disorders
ABDOMINAL PAINGastrointestinal disorders
ASPARTATE AMINOTRANSFERASE INCREASEDInvestigations
DIARRHEAGastrointestinal disorders
DYSGEUSIANervous system disorders
INSOMNIAPsychiatric disorders
WEIGHT LOSSInvestigations
BACK PAINMusculoskeletal and connective tissue disorders
HYPOMAGNESEMIAMetabolism and nutrition disorders
HYPONATREMIAMetabolism and nutrition disorders
PLATELET COUNT DECREASEDInvestigations
ALOPECIASkin and subcutaneous tissue disorders
ANXIETYPsychiatric disorders
EDEMA LIMBSGeneral disorders
FALLInjury, poisoning and procedural complications
HEADACHENervous system disorders
HYPERGLYCEMIAMetabolism and nutrition disorders
HYPOPHOSPHATEMIAMetabolism and nutrition disorders
PAIN IN EXTREMITYMusculoskeletal and connective tissue disorders
ALANINE AMINOTRANSFERASE INCREASEDInvestigations
ALKALINE PHOSPHATASE INCREASEDInvestigations
COUGHRespiratory, thoracic and mediastinal disorders
DEHYDRATIONMetabolism and nutrition disorders
DRY MOUTHGastrointestinal disorders
DYSPHAGIAGastrointestinal disorders
HYPOKALEMIAMetabolism and nutrition disorders
HYPOTENSIONVascular disorders
LYMPHOCYTE COUNT DECREASEDInvestigations
PARESTHESIANervous system disorders
PERIPHERAL SENSORY NEUROPATHYNervous system disorders

Most-reported serious reactions: SEPSIS, BACK PAIN, DYSPNEA, FEBRILE NEUTROPENIA, LOWER GASTROINTESTINAL HEMORRHAGE.

Data from ClinicalTrials.gov NCT03913455 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Epigenetics-targeted drugs: current paradigms and future challenges.
    Dai W, Qiao X, Fang Y, Guo R, et al · · 2024 · cited 131× · PMID 39592582 · DOI 10.1038/s41392-024-02039-0
  2. Novel Approaches to Epigenetic Therapies: From Drug Combinations to Epigenetic Editing.
    Majchrzak-Celińska A, Warych A, Szoszkiewicz M. · · 2021 · cited 85× · PMID 33572577 · DOI 10.3390/genes12020208
  3. Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.
    Song J, Yang P, Chen C, Ding W, et al · · 2025 · cited 40× · PMID 40675967 · DOI 10.1038/s41392-025-02266-z
  4. Targeting Epigenetics in Lung Cancer.
    Chao YL, Pecot CV. · · 2021 · cited 28× · PMID 32900703 · DOI 10.1101/cshperspect.a038000
  5. How metabolism bridles cytotoxic CD8<sup>+</sup> T cells through epigenetic modifications.
    Van Acker HH, Ma S, Scolaro T, Kaech SM, et al · · 2021 · cited 24× · PMID 33867272 · DOI 10.1016/j.it.2021.03.006
  6. Mechanisms of drugs-resistance in small cell lung cancer: DNA-related, RNA-related, apoptosis-related, drug accumulation and metabolism procedure.
    Chen P, Kuang P, Wang L, Li W, et al · · 2020 · cited 24× · PMID 32676338 · DOI 10.21037/tlcr-19-547
  7. Clinical Perspectives to Overcome Acquired Resistance to Anti-Programmed Death-1 and Anti-Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer.
    Lee YJ, Lee JB, Ha SJ, Kim HR. · · 2021 · cited 16× · PMID 34001680 · DOI 10.14348/molcells.2021.0044
  8. Research progress and applications of epigenetic biomarkers in cancer.
    Gao J, Shi W, Wang J, Guan C, et al · · 2024 · cited 10× · PMID 38681199 · DOI 10.3389/fphar.2024.1308309

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