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A Two Part Study of RO6870810. Dose-Escalation Study in Participants With Advanced Solid Tumors and Expansion Study in Participants With Selected Malignancies

NCT01987362

Description:

This is a Phase 1, non-randomized, dose-escalating, open label, multi-center study to be conducted in two parts (Part A and Part B). RO6870810 is a small molecule, non-covalent inhibitor of bromodomain and extra-terminal (BET) family of bromodomains. This study is designed to characterize the safety, tolerability, pharmacokinetics and anti-tumor activity of RO6870810 in participants with histologically confirmed solid tumors with progressive disease (PD) which is refractory or intolerant to standard/approved therapies. In Part A, RO6870810 will be administered by subcutaneous (SC) injection daily for either 21 consecutive days in a 28-day cycle or for 14 consecutive days in a 21-day treatment cycle in participants with advanced solid tumor malignancies to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT). In Part B, RO6870810 will be administered at a dose up to the MTD to further characterize the safety profile and biological effect in a subset of participants with advanced solid tumor malignancies. It is anticipated that a total of 84 participants will be enrolled in to this study (54 in Part A and 30 in Part B). In addition, it is expected that up to 20 participants with histologically confirmed nuclear protein in testis (NUT)-midline carcinoma (NMC) with progressive disease requiring therapy will be enrolled in the sub-study of Parts A and B. In addition, up to 20 participants with diffuse large B-cell lymphoma (DLBCL) may be enrolled at selected study sites.

Related Conditions:
  • Malignant Solid Tumor
  • NUT Midline Carcinoma of the Head and Neck
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

A Two Part, Multicenter, Open-label Study of TEN-010 Given Subcutaneously

Title

  • Brief Title: A Two Part, Multicenter, Open-label Study of TEN-010 Given Subcutaneously
  • Official Title: A Two Part, Phase 1, Multicenter, Open-label Study of TEN-010 Given Subcutaneously. Part A: A Dose-Escalation Study in Patients With Advanced Solid Tumors. Part B: An Expansion Cohort in Patients With Selected Malignancies.
  • Clinical Trial IDs

    NCT ID: NCT01987362

    ORG ID: TEN-010-001

    Trial Conditions

    Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    TEN-010 Treatment

    Trial Purpose

    TEN-010 is a small molecule, bromodomain and extra-terminal domain (BET) bromodomain
    inhibitor. This study is designed to characterize the safety, tolerability, pharmacokinetics
    and anti-tumor activity of TEN-010 in patients who are refractory or intolerant to
    standard/approved therapies. This first-in-human study of TEN-010 will be conducted in two
    parts: dose escalation and dose expansion. For dose escalation (Part A), a standard "3+3"
    design will be used in which successive cohorts of three or more patients with advanced
    solid tumor malignancies will be treated at escalating doses until a maximum tolerated dose
    (MTD) is identified. For the dose expansion part of the study (Part B), a subset of patients
    with advanced solid malignancies will be treated with TEN-010 at the MTD (or the highest
    dose tested if the MTD is not defined) to further characterize safety and biological effect.
    In addition, up to 10 patients with nuclear protein in testis (NUT) midline carcinoma (NMC)
    will be permitted to enroll in a substudy of the protocol.

    Detailed Description

    This is a Phase 1 non-randomized, dose-escalating, open label, multi-center study to be
    conducted in two parts (Part A and Part B). A maximum of 56 patients aged 18 years or older
    with histologically confirmed advanced solid tumors with progressive disease requiring
    therapy will be enrolled in the study. It is expected that approximately 36 patients will be
    enrolled in 6 cohorts of up to 6 patients per cohort in Part A of the study and 20
    additional patients will be enrolled in Part B of the study. Up to 10 patients with NMC may
    be enrolled as part of a substudy within the protocol.

    Trial Arms

    Name Type Description Interventions
    Treatment Experimental TEN-010 TEN-010

    Eligibility Criteria

    INCLUSION CRITERIA

    General

    - Patients with solid tumors must have one or more metastatic tumors evaluable or
    measurable on radiographic imaging

    - Ambulatory patients >= 18 years of age

    - ECOG performance status of 0 or 1 (or 2 upon approval by the medical monitor)

    - Life expectancy of >= 3 months

    - Disease-free of active second/secondary or prior malignancies >= 2 years with the
    exception of currently treated basal cell, squamous cell carcinoma of the skin, or
    carcinoma "in-situ" of the cervix or breast

    - Adequate hematological, renal, hepatic and coagulation laboratory test results.

    - Women of child bearing potential and men must agree to use adequate contraception
    during the study and for 4 months after the last dose of study drug.

    - Available for the duration of the study and willing to follow study procedures

    - Provide written informed consent

    Advanced Solid Malignancies

    - Patients with previously treated, histologically confirmed advanced solid malignancy
    with progressive disease requiring therapy

    - Patients must be refractory or intolerant to standard therapy

    NUT-midline carcinoma

    - Patients with histologically confirmed newly diagnosed or relapsed/refractory
    NUT-midline carcinoma (NMC) with progressive disease requiring therapy

    - Diagnosis of one of the following is required:

    1. NUT Midline Carcinoma based on ectopic expression of NUT protein as determined
    by Immunohistochemistry (IHC) and/or;

    2. Detection of NUT gene translocation as determined by Fluorescence In-Situ
    Hybridization (FISH).

    EXCLUSION CRITERIA

    - Patients with hematologic malignancies

    - New York Heart Association Class III or IV, cardiac disease, myocardial infarction
    within the past 6 months, unstable arrhythmia

    - Have QTcF > 470 msec (female) or > 450 (male), or history of congenital long QT
    syndrome

    - Active, uncontrolled bacterial, viral, or fungal infections

    - Known clinically important respiratory impairment

    - Positive for HIV, hepatitis B surface antigen, or hepatitis C antibodies

    - History of major organ transplant

    - History of an autologous or allogeneic bone marrow transplant

    - Symptomatic central nervous system malignancy or metastasis

    - Pregnant or nursing

    - Treatment with surgery or chemotherapy within 28 days prior to study entry

    - Prior treatment with small molecule (BET) family inhibitor

    - Radiation for symptomatic lesions within 14 days of study enrollment

    - Other exclusions apply

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum tolerated dose and dose-limiting toxicities as determined in Part A.

    Safety parameters

    Secondary Outcome Measures

    Pharmacokinetics

    Efficacy

    Trial Keywords

    advanced solid tumors