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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-02-04

Study Completion Date

2017-04-18

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Golidocitinib With PD-1 Inhibitors as Maintenance Treatment for Previously Untreated ES-SCLC

NCT07110103

SCLC SCLC, Extensive Stage

NOT_YET_RECRUITING PHASE2

Anti-GPC3 CAR T for Recurrent or Refractory Lung Squamous Cell Carcinoma

NCT02876978

Lung Squamous Cell Carcinoma

UNKNOWN PHASE1

Phase II Efficacy Study of Repotrectinib in Frail and/or Elderly Patients With ROS1-rearranged Advanced NSCLC

NCT06552234

NSCLC Stage IV NSCLC, Stage III

RECRUITING PHASE2

A Study of Lorlatinib in Subjects With ROS1-Positive Non-Small Cell Lung Cancer

NCT05297890

Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer

ACTIVE_NOT_RECRUITING PHASE2

Molecular Determinants of Acquired Clinical Resistance to Crizotinib in Non-small Cell Lung Cancer Harboring a Translocation or Inversion Event Involving the ALK Gene Locus

NCT01300429

Lung Cancer

COMPLETED

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Carcinoma, Small Cell

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Dose Escalation Cohort

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).The dose escalation will complete when RP2D is determined. The RP2D will be the MTD or a lower dose that provides adequate PK exposure and biologic activity with superior tolerability.

Group Type EXPERIMENTAL

GSK2879552

Intervention Type DRUG

Subjects will receive GSK2879552orally with approximately 200 milliliter (mL) of water.

Dose Expansion Cohort

Once the RP2D has been determined, an expansion cohort of up to 30 subjects will be enrolled in order to better characterize the clinical activity and safety profile of the RP2D

Group Type EXPERIMENTAL

GSK2879552

Intervention Type DRUG

Subjects will receive GSK2879552orally with approximately 200 milliliter (mL) of water.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

GSK2879552

Subjects will receive GSK2879552orally with approximately 200 milliliter (mL) of water.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No