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Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations

NCT02383927

Description:

Phase II study to investigate the antitumor activity in terms of objective response rate (ORR) of tipifarnib in subjects with advanced tumors that carry HRAS mutations and for whom there is no standard curative therapy available. Note; Only cohort 2 (Head & Neck SCC) and cohort 3 (Other SCC) are currently open

Related Conditions:
  • Malignant Solid Tumor
  • Malignant Thyroid Gland Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Phase II Study of <span class="go-doc-concept go-doc-intervention">Tipifarnib</span> in Advanced Cancers With <span class="go-doc-concept go-doc-biomarker">HRAS</span> <span class="go-doc-concept go-doc-keyword">Mutations</span>

Title

  • Brief Title: Phase II Study of Tipifarnib in Advanced Cancers With HRAS Mutations
  • Official Title: An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies With HRAS Mutations
  • Clinical Trial IDs

    NCT ID: NCT02383927

    ORG ID: KO-TIP-001

    Trial Conditions

    Thyroid Cancer

    Advanced Non-hematological Malignancies

    HRAS Mutant Tumor

    Trial Interventions

    Drug Synonyms Arms
    Tipifarnib Zarnestra Cohort 1, Cohort 2

    Trial Purpose

    Phase II study to investigate the antitumor activity in terms of ORR of tipifarnib in
    subjects with advanced tumors that carry HRAS mutations and for whom there is no standard
    curative therapy available.

    Detailed Description

    This Phase II study will investigate the antitumor activity in terms of ORR of tipifarnib in
    subjects with locally advanced, unresectable or metastatic, relapsed and/or refractory
    tumors that carry HRAS mutations and for whom there is no curative therapy available.
    Subject with information available on tumor HRAS status previously generated are eligible.
    All subjects must consent to provide at least 10 tumor slides from a prior diagnostic biopsy
    for a retrospective testing of RAS gene status at a central facility.

    Subjects will be enrolled into two nonrandomized cohorts:

    - Cohort 1: Malignant thyroid tumors with HRAS mutations.

    - Cohort 2: Non-hematological malignancies with HRAS mutations.

    Trial Arms

    Name Type Description Interventions
    Cohort 1 Experimental Thyroid Cancer Tipifarnib
    Cohort 2 Experimental Non-hematological malignancies Tipifarnib

    Eligibility Criteria

    Inclusion Criteria:

    - histologically or cytologically confirmed diagnosis of non-hematological malignancy
    for which there is no curative therapy available.

    - tumor that carries a missense HRAS mutation

    - Subject consents to provide at least 10 unstained tumor slides for retrospective
    testing of HRAS gene tumor status

    - Subject has measurable disease according to RECIST v1.1 and has relapsed or is
    refractory to prior therapy.

    - At least 2 weeks since the last systemic therapy or radiotherapy regimen prior to
    enrolment

    - ECOG PS 0 or 1

    - Acceptable liver function

    - Acceptable renal function

    - Acceptable hematologic status

    Exclusion Criteria:

    - Prior treatment with an FTase inhibitor

    - History of relevant coronary heart disease or myocardial infarction within last 3
    years, NYHA Grade III or greater congestive heart failure, cerebro-vascular attack
    within the prior year, or serious cardiac arrhythmia requiring medication except
    atrial fibrillation.

    - Known uncontrolled brain, leptomeningeal or epidural metastases (unless treated and
    well controlled for at least 4 weeks prior to Cycle 1 Day 1). Controlled brain
    metastases that require continuous high dose corticosteroid use within 4 weeks of Day
    1.

    - Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms
    within 4 weeks first dose

    - Major surgery, other than diagnostic surgery, within 4 weeks prior to first dose,
    without complete recovery.

    - Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
    therapy. Known infection with HIV, or an active infection with hepatitis B or
    hepatitis C

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Objective Response Rate (ORR)

    Secondary Outcome Measures

    Progression-free Survival (PFS)

    Duration of Response (DOR)

    Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Trial Keywords