Clinical Trials /

First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies

NCT01971515

Description:

This is a Phase 1, first-in-human, open-label, non-randomized, dose escalation, trial to explore the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and clinical activity signals of MSC2363318A.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies

Title

  • Brief Title: First-in-Human Dose Escalation Trial in Subjects With Advanced Malignancies
  • Official Title: A Phase I, First-in-Human, Dose Escalation Trial of MSC2363318A, a Dual p70S6K/Akt Inhibitor, in Subjects With Advanced Malignancies
  • Clinical Trial IDs

    NCT ID: NCT01971515

    ORG ID: EMR100018-001

    Trial Conditions

    Solid Tumor

    Trial Interventions

    Drug Synonyms Arms
    MSC2363318A M2698 MSC2363318A

    Trial Purpose

    This is a Phase 1, first-in-human, open-label, non-randomized, dose escalation, trial to
    explore the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and clinical
    activity signals of MSC2363318A.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    MSC2363318A Experimental MSC2363318A

    Eligibility Criteria

    Inclusion Criteria:

    - Age greater than or equal to (>=)18 years

    - Confirmed diagnosis of advanced solid tumor that may be controlled with p70S6K or Akt
    inhibition based on the presence of already identified or potentially present
    molecular alteration known or likely to affect the phosphoinositide 3-Kinase (PI3K)
    pathway, such as: phosphate and tensin homolog (PTEN), phosphoinositide 3-Kinase
    catalytic subunit alpha isoform (PI3KCA), protein kinase B (Akt), mammalian target of
    rapamycin (mTOR), tumor sclerosis complex 1 (TSC1), tumor sclerosis complex 2 (TSC2),
    epidermal growth factor receptor (ErbB1) (EGFR), human epidermal growth factor
    receptor 2 (ErbB2), and liver kinase B1 (LKB1), and for which the subject had
    previously been offered an approved therapy no standard curative or palliative
    measures exist, or such available measures are not acceptable to the subject. In
    particular:

    1. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer subjects
    must have progressed on or have been intolerant to at least 2 lines of
    HER2-directed therapy, and

    2. Epidermal growth factor receptor (EGFR)-mutation positive lung cancer subjects
    must have progressed on or have been intolerant to an EGFR inhibitor

    - Measurable disease using clinically appropriate criteria for the type of malignancy,
    RECIST version 1.1 for solid tumors and Cheson 2007 for lymphoma

    - A tumor accessible for biopsies and consent to undergo tumor biopsies before and
    during MSC2363318A treatment

    - Ability to read and understand the informed consent form and willingness and ability
    to give informed consent and demonstrate comprehension of the trial before undergoing
    any trial activities

    - Negative blood pregnancy test at the screening visit for women of childbearing
    potential

    - Willingness to avoid pregnancy and breast feeding beginning two weeks before the
    first MSC2363318A dose and ending three months after the last trial treatment. Male
    subjects with female partners of childbearing potential and female subjects of
    childbearing potential must use adequate contraception in the judgment of the
    Investigator, such as a two barrier method or a one barrier method with spermicide or
    intrauterine device

    Exclusion Criteria:

    - Eastern Cooperative Oncology Group Performance Status >=2

    - Previous therapy with:

    - Chemotherapy, immunotherapy, hormonal therapy (except low dose corticosteroids),
    biologic therapy, or any other anticancer therapy within 28 days (or five
    elimination half-lives for noncytotoxics, whichever is shorter) of Day 1 of
    trial drug treatment (6 weeks for nitrosureas or mitomycin

    - Any investigational agent within 28 days of Day 1 of trial drug treatment

    - Extensive prior radiotherapy on more than 30 percent of bone marrow reserves, or
    prior bone marrow/stem cell transplantation within 5 years from enrollment

    - Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to
    baseline or Grade 1 or less

    - Major surgical intervention or participation in a therapeutic clinical trial within
    28 days from Day 1 of the first dose of MSC2363318A

    - Bone marrow impairment, renal impairment, liver function abnormality and impaired
    cardiac function as defined in the protocol

    - History of cerebral vascular accident or stroke within the previous 2 years

    - Uncontrolled hypertension

    - Known active central nervous system (CNS) metastases (unless stable by computed
    tomography [CT] scan for at least 1 month without evidence of cerebral edema and no
    requirements for corticosteroids or anticonvulsants)

    - History of difficulty swallowing, malabsorption or other chronic gastrointestinal
    disease or conditions that may hamper compliance and/or absorption of the
    investigational product

    - Known human immunodeficiency virus, viral hepatitis, or tuberculosis positivity

    - Legal incapacity or limited legal capacity

    - Any other condition which, in the opinion of the Investigator, might impair the
    subject's tolerance of trial treatment, the safety of the individual subject or the
    outcome of the trial

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of dose limiting toxicities (DLTs)

    Secondary Outcome Measures

    Pharmacodynamic marker level of ribosomal protein S6 (RPS6) phosphorylation in blood and tumor tissue

    Change in glucose metabolism as assessed by fluorodeoxyglucose positron emission tomography /computed tomography (FDG PET/CT) in target lesions

    Pharmacokinetics parameters: Cmax, Tmax, AUC (0-tau), AUC (0-t), AUC (0-infinity), T(1/2), CL/f, CLss/f, Vz/f, Vss/f, Racc (AUC), Racc (Cmax), CLR, Ae (0-tau)

    Number of subjects with best overall response according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v 1.1) or Cheson 2007

    Percentage of subjects with clinical benefit

    Number of subjects with Treatment-emergent adverse events (TEAEs)

    Trial Keywords

    MSC2363318A

    Maximum tolerated dose

    Dose limiting toxicities

    Recommended phase 2 dose

    M2698