Clinical Trials /

A Phase I/IIa Open-Label, Dose Escalation and Cohort Expansion Trial of Oral TSR-011 in Patients With Advanced Solid Tumors and Lymphomas

NCT02048488

Description:

TSR-011 is a potent small molecule inhibitor of tyrosine kinases involved in cancer, including: 1. Anaplastic lymphoma kinase (ALK) 2. The tropomyosin-related kinases TRKA, TRKB, and TRKC This is a sequential, open-label, non-randomized study with dose escalation in Phase 1, followed by expansion at a recommended phase 2 dose.

Related Conditions:
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

A Phase I/IIa Open-Label, Dose Escalation and Cohort Expansion Trial of Oral <span class="go-doc-concept go-doc-intervention">TSR-011</span> in Patients With Advanced Solid Tumors and Lymphomas

Title

  • Brief Title: A Phase I/IIa Open-Label, Dose Escalation and Cohort Expansion Trial of Oral TSR-011 in Patients With Advanced Solid Tumors and Lymphomas
  • Official Title: A Phase I/IIa Open-Label, Dose Escalation and Cohort Expansion Trial of Oral TSR-011 in Patients With Advanced Solid Tumors and Lymphomas
  • Clinical Trial IDs

    NCT ID: NCT02048488

    ORG ID: PR-20-5006-C

    Trial Conditions

    Solid Tumors

    Lymphomas

    Trial Interventions

    Drug Synonyms Arms
    TSR-011 ALK inhibitor, ALKi, TRK inhibitor Experimental Drug TSR-011

    Trial Purpose

    TSR-011 is a potent small molecule inhibitor of tyrosine kinases involved in cancer,
    including:

    1. Anaplastic lymphoma kinase (ALK)

    2. The tropomyosin-related kinases TRKA, TRKB, and TRKC

    This is a sequential, open-label, non-randomized study with dose escalation in Phase 1,
    followed by expansion at a recommended phase 2 dose.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Experimental Drug TSR-011 Experimental Experimental Drug TSR-011 TSR-011

    Eligibility Criteria

    Inclusion Criteria:

    - To be considered eligible to participate in this study, all of the following
    requirements must be met:

    1. Patients in Phase 1 must have metastatic or locally advanced solid tumors who
    have failed to respond to standard therapy

    2. All patients must have confirmation of either ALK positive or TRK positive
    status.

    3. Patients in Phase 1 will not be required to have measurable disease. All
    patients in Phase 2a will be required to have measurable disease by RECIST.

    4. All patients enrolled in this study must have tumor tissue available.

    5. Patient (male or female) must be 18 years of age (except where age of majority
    is 16 years in a particular country, such as the United Kingdom).

    6. Patient must have performance status 2 on the ECOG Performance Scale.

    7. Patient must have an estimated life expectancy of at least 3 months.

    8. Patients must have adequate organ function.

    9. For patients previously treated with myelosuppressive therapy, at least 3 weeks
    must have elapsed and toxicity must have recovered to grade 1 or baseline.
    Non-myelosuppressive therapy patients must have recovered from all
    treatment-related toxicities. Fourteen days must have elapsed since palliative
    radiation for bone metastasis.

    10. Female patients of childbearing potential must have a negative serum pregnancy
    test and use adequate birth control for the duration of study participation and
    for 3 months after the last dose of study drug.

    11. The patient or his or her legal representative must be able to read, understand,
    and provide signed informed consent.

    12. Patient is able to understand the study procedures and agrees to participate in
    the study by giving written informed consent.

    Exclusion Criteria:

    - Patients will not be deemed eligible for entry into this study if any of the
    following criteria are met:

    1. Patient has leukemia.

    2. Patient is a pregnant or lactating female.

    3. Patient has uncontrolled congestive heart failure, angina, or has had a
    myocardial infarction in the preceding 3 months.

    4. Ongoing cardiac dysrhythmias of NCI CTCAE Grade 2, atrial fibrillation of any
    grade, or QTc interval >450 msec.

    5. Patients with risk factors for Torsade de point and patients receiving
    concomitant medication with QT-prolonging medicines.

    6. Patient has an uncontrolled concurrent medical condition or disease.

    7. Patient has undergone bone marrow or stem cell transplantation in the past 6
    months.

    8. Patient has a known hypersensitivity to the components of TSR-011 or the
    excipients.

    9. Patient has active or uncontrolled infection.

    10. Patient has a known psychiatric or substance abuse disorder.

    11. Patient has active second primary malignancy.

    12. Patient is observed to have a clinically active central nervous system (CNS)
    metastases or carcinomatous meningitis.

    13. Patient has any other severe concurrent disease which, in the judgment of the
    Investigator, would preclude study participation.

    14. Patient is known to be HIV positive or who has an AIDS-related illness.

    15. Patient has a known history of or active (treated or not) Hepatitis B or C.

    16. Patient has presence of ascites causing significant symptoms.

    17. A patient must stop taking any prescription, over-the-counter, or herbal remedy
    known to be an inhibitor or inducer of CYP3A4/5.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of Adverse Events (AEs)

    Secondary Outcome Measures

    Area Under the Concentration-Time Curve (AUC)

    Maximum Tolerated Dose (MTD)

    Response Rate (RR)

    Dose limiting toxicity (DLT)

    Progression Free Survival (PFS)

    Recommended Phase 2 Dose (RP2D)

    Trial Keywords

    non small cell lung cancer

    NSCLC

    Anaplastic lymphoma kinase

    ALK tyrosine kinase receptor

    ALK+

    TRK+

    ALK inhibitor

    TRK inhibitor

    tropomyosin receptor kinase

    TRKA

    TRKB

    TRKC

    advanced malignancy