Last updated: 07/17/2024 17:03:53

Investigation of GSK2879552 in Subjects with Relapsed/Refractory Small Cell Lung Carcinoma

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GSK study ID
200858
See study documents
Clinicaltrials.gov ID
NCT02034123
See results summary
EudraCT ID
2013-003451-38
EU CT Number
Not applicable
Trial status
Other
Other
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Phase I Open-label, Dose Escalation Study to Investigate The Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2879552 Given Orally in Subjects with Relapsed/Refractory Small Cell Lung Carcinoma
Trial description: GSK2879552 is a potent, selective, mechanism-based inactivator of Lysine Specific Demethylase 1 (LSD1)/ CoRepressor for Element-1-Silencing Transcription factor (CoREST) activity. This is a phase I, open-label, multi-center, non-randomized, 2-part first time in human (FTIH) study for GSK2879552. Part 1 is a dose escalation phase to determine the recommended phase 2 dose (RP2D) for GSK2879552 based on the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) profiles observed after oral administration of GSK2879552. Any dose level(s) may be expanded up to 12 subjects in order to collect additional data on PK and PD.The safety and PK/PD data will be reviewed prior to the dose decision, and the dose escalation will be guided by the Neuenschwander -continuous reassessment method (N-CRM). Built-in safety constraints are in place to prevent exposing subjects to undue risk of toxicity. Once RP2D is identified, an expansion cohort (Part 2) of up to 30 subjects will be enrolled to further evaluate the clinical activity and tolerability of GSK2879552 in subjects with relapsed/refractory SCLC.
Primary purpose:
Treatment
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Part 1: Number of participants with serious adverse events (SAEs) and non-SAEs

Timeframe: Median of 7.286 weeks of drug exposure

Part 1: Number of participants with dose limiting toxicities (DLT)

Timeframe: Median of 7.286 weeks of drug exposure

Part 1: Number of participants with dose reduction or delays

Timeframe: Median of 7.286 weeks of drug exposure

Part 1: Number of participants withdrawn due to toxicities

Timeframe: Median of 7.286 weeks of drug exposure

Part 1: Number of participants with change in clinical chemistry toxicity grade from Baseline

Timeframe: Baseline and median of 7.286 weeks of drug exposure

Part 1: Number of participants with change in hematology toxicity grade from Baseline

Timeframe: Baseline and median of 7.286 weeks of drug exposure

Part 1:Number of participants with critical changes in values of vital signs in response to drug

Timeframe: Median of 7.286 weeks of drug exposure

Part 1: Number of participants with abnormal findings for electrocardiogram (ECG) parameters

Timeframe: Median of 7.286 weeks of drug exposure

Part 1: Number of participants with abnormal findings undergoing physical examinations

Timeframe: Median of 7.286 weeks of drug exposure

Part 2: Number of participants achieving disease control rate at Week 16

Timeframe: Week 16

Secondary outcomes:

Part 1: Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC [0-t]) following single and repeat dose administration of GSK2879552

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Part 1: Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC [0-infinity]) following single dose administration of GSK2879552

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1

Part 1: Area under the concentration-time curve over the dosing interval (AUC [0-tau]) following repeat dose administration of GSK2879552

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 15

Part 1: Maximum observed plasma concentration (Cmax) following single and repeat dose administration of GSK2879552

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Part 1: Time to reach Cmax (Tmax) following single and repeat dose administration of GSK2879552

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Part 1: Apparent terminal phase elimination rate constant (lambda z) following single and repeat dose administration of GSK2879552

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Part 1: Apparent terminal phase half-life (T1/2) following single and repeat dose administration of GSK2879552

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Part 1: Accumulation ratio following administration of GSK2879552

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Part 1: Time invariance ratio following administration of GSK2879552

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Part 1: Number of participants achieving disease control rate at Week 16

Timeframe: Week 16

Part 1 :Median effective dose (ED50) of GSK2879552 with respect to platelet nadir as percent change from Baseline and dose

Timeframe: Baseline and median of 7.286 weeks of drug exposure

Part 1: ED50 of GSK2879552 with respect to platelet nadir as percent change from Baseline and Cmax

Timeframe: Baseline and median of 7.286 weeks of drug exposure

Part 1: ED50 of GSK2879552 with respect to platelet nadir as percent change from Baseline and AUC (0 to infinity)

Timeframe: Baseline and median of 7.286 weeks of drug exposure

Part 2: Number of participants with SAEs and non-SAEs

Timeframe: Up to 2 years

Part 2: Number of participants with DLTs

Timeframe: Up to 2 years

Part 2: Number of participants with dose reduction or delays

Timeframe: Up to 2 years

Part 2: Number of participants withdrawn due to toxicities

Timeframe: Up to 2 years

Part 2: Number of participants with change in clinical chemistry toxicity grade from Baseline

Timeframe: Baseline and up to 2 years

Part 2: Number of participants with change in hematology toxicity grade from Baseline

Timeframe: Baseline and up to 2 years

Part 2:Number of participants with critical changes in values of vital signs in response to drug

Timeframe: Up to 2 years

Part 2: Number of participants with abnormal findings for ECG parameters

Timeframe: Up to 2 years

Part 2: Number of participants with abnormal findings undergoing physical examinations

Timeframe: Up to 2 years

Part 2: Clearance following administration of GSK2879552

Timeframe: Pre-dose, 0.5, and 3 hours post-dose on Day 1; Pre-dose on Day 8; Pre-dose, 0.5 to 1 hour, and 4 to 6 hours on Day 15; Pre-dose at Day 22 and up to every 4 weeks until Week 48

Part 2: Volume of distribution following administration of GSK2879552

Timeframe: Pre-dose, 0.5, and 3 hours post-dose on Day 1; Pre-dose on Day 8; Pre-dose, 0.5 to 1 hour, and 4 to 6 hours on Day 15; Pre-dose at Day 22 and up to every 4 weeks until Week 48

Part 2: ED50 of GSK2879552 with respect to platelet nadir as percent change from Baseline and dose

Timeframe: Baseline and up to 2 years

Part 2: ED50 of GSK2879552 with respect to platelet nadir as percent change from Baseline and Cmax

Timeframe: Baseline and up to 2 years

Part 2: ED50 of GSK2879552 with respect to platelet nadir as percent change from Baseline and AUC (0 to infinity)

Timeframe: Baseline and Up to 2 years

Part 2: Duration of response

Timeframe: Up to 2 years

Part 2: Progression free survival (PFS)

Timeframe: Up to 2 years

Part 2: Percentage of participants achieving CR and PR

Timeframe: Up to 2 years

Interventions:
  • Drug: GSK2879552
    • Enrollment:
    29
    Primary completion date:
    2017-18-04
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Todd M. Bauer, Benjamin Besse, Alex Martinez-Marti, Jose Manuel Trigo, Victor Moreno, Pilar Garrido, Geraldine Ferron-Brady, Yuehui Wu, Jennifer Park, Therese Collingwood, Ryan G. Kruger, Helai P. Mohammad, Marc S. Ballas, Arindam Dhar, Ramaswamy Govindan. A phase I open-label, dose escalation study of the safety, pharmacokinetics, pharmacodynamics and efficacy of GSK2879552 in relapsed/refractory small cell lung cancer. J Thorac Oncol. 2019;1410(10):1828-1838 DOI: 10.1016/j.jtho.2019.06.021 PMID: 31260835
    Medical condition
    Carcinoma, Small Cell
    Product
    GSK2879552
    Collaborators
    Not applicable
    Study date(s)
    February 2014 to April 2017
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Provided signed written informed consent
    • Males and females >=18 years of age (at the time consent is obtained).
    • Concurrent malignancy other than SCLC. History of other malignancy is allowed as long as there is no evidence of active disease or need for treatment.
    • Currently receiving anti-cancer therapy. Exceptions: Zoledronic acid and denosumab to treat bone metastasis are allowed.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Provided signed written informed consent
    • Males and females >=18 years of age (at the time consent is obtained).
    • Histologically or cytologically confirmed diagnosis of small cell lung carcinoma. Subjects must have measurable disease per RECIST 1.1 (for Part 2 only).
    • Recurrent or refractory disease after receiving at least one prior standard/approved platinum-containing chemotherapy regimen, or where standard therapy is refused. Part 2 only: Subjects must have recurrent disease after receiving a maximum of two prior chemotherapy regimens including at least one platinum containing regimen.
    • Eastern Cooperative Oncology Group (ECOG) performance status of <= 1. (ECOG performance status of 0 or 1).
    • Tumor tissue requirements: Availability of archival tissue, or willingness to undergo fresh biopsy at baseline; Enrollment in PK/PD cohort may be limited to subjects with disease amenable to pre- and post-dose biopsies, and willingness to undergo biopsy.
    • All prior treatment-related toxicities must be National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 <=Grade 1 at the time of enrollment (except for alopecia)
    • Adequate baseline organ function
    • Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, as defined in protocol, during the study and for 7 days following the last dose of study treatment.
    • Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described in protocol from the administration of the first dose of study treatment until 3 months after the last dose of study treatment to allow for clearance of any altered sperm.
    • Able to swallow and retain orally administered study treatment and does not have any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
    • French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
    Exclusion criteria:
    • Concurrent malignancy other than SCLC. History of other malignancy is allowed as long as there is no evidence of active disease or need for treatment.
    • Currently receiving anti-cancer therapy. Exceptions: Zoledronic acid and denosumab to treat bone metastasis are allowed.
    • Prior treatment with temozolomide, dacarbazine or procarbazine.
    • Prior treatment with poly ADP ribose polymerase (PARP) inhibitors (e.g., olaparib, ABT-888).
    • Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower.
    • Received major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK2879552 administration. Chemotherapy regimens with delayed toxicity within the last four weeks (six weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity or palliative radiation to a limited area within the last two weeks.
    • Administration of an investigational drug within 28 days or 5 half-lives, whichever is shorter preceding the first dose of study treatment(s) in this study.
    • French subjects: The French subject has participated in any study using an investigational study treatment(s) during the previous 28 days.
    • Subjects with current/a history of bleeding disorder or coagulopathy or who are at particularly high risk for bleeding complications.
    • Requiring anticoagulants at therapeutic doses or platelet inhibitor.
    • Current use of a prohibited medication or expected to require any of these medications during treatment with the investigational drug
    • Evidence of severe or uncontrolled systemic diseases. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator
    • Known active Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infections. Subjects with laboratory evidence of HBV clearance may be enrolled
    • Leptomeningeal metastases or spinal cord compression due to disease.
    • Subjects with previously untreated or uncontrolled brain metastases.
    • Cardiac abnormalities
    • Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2879552 or LSD1 inhibitors that contraindicates their participation.
    • Lactating female
    • Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice, pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study treatment(s) until the last dose of study drug.

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    Barcelona, Spain, 08035
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Columbus, Ohio, United States, 43210
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Madrid, Spain, 28034
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Madrid, Spain, 28040
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Málaga, Spain, 29010
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Nashville, Tennessee, United States, 37203
    Status
    Study Complete
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    Showing 1 - 6 of 8 Results

    Study documents

    Clinical study report
    Available language(s): English
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    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Other
    Actual primary completion date
    2017-18-04
    Actual study completion date
    2017-18-04

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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