Investigation of GSK2879552 in Subjects With Relapsed/Refractory Small Cell Lung Carcinoma
Condition: Carcinoma, Small Cell
MeSH terms: Carcinoma; Lung Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Small Cell
Intervention: GSK2879552
Intervention description: Subjects will receive GSK2879552orally with approximately 200 milliliter (mL) of water.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: First time in humans; Small cell lung carcinoma; Oncology; GSK2879552; LSD1 inhibitor

Summary:

      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.
    

Eligibility 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.