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Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy

NCT03719690

Description:

An international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN). The first cohort will assess the objective response rate (ORR) of tipifarnib in subjects with HNSCC with HRAS mutations. The second study cohort, SEQ-HN, is an observational sub-study and includes 2 types of patients: (1) the historical record of first line therapy in subjects with HRAS mutant HNSCC participating in Cohort 1 in whom first line outcome data are available and (2) matched control HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT03719690

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy
  • Official Title: A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC) With HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN)

Clinical Trial IDs

  • ORG STUDY ID: KO-TIP-007
  • NCT ID: NCT03719690

Conditions

  • HRAS Gene Mutation
  • HNSCC

Interventions

DrugSynonymsArms
TipifarnibAIM-HN

Purpose

An international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN). The first cohort will assess the objective response rate (ORR) of tipifarnib in subjects with HNSCC with HRAS mutations. The second study cohort, SEQ-HN, is an observational sub-study and includes 2 types of patients: (1) the historical record of first line therapy in subjects with HRAS mutant HNSCC participating in Cohort 1 in whom first line outcome data are available and (2) matched control HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.

Detailed Description

      KO-TIP-007 is an international, multicenter, open-label, 2 cohort, non-comparative, pivotal
      study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN) and the impact of
      HRAS mutations on response to first line systemic therapies for HNSCC (SEQ-HN). KO-TIP-007
      has 2 study cohorts. The first study cohort, named AIM-HN, includes HNSCC subjects with HRAS
      mutations. AIM-HN subjects will receive treatment with tipifarnib and the outcome of this
      cohort will be evaluated for ORR by an independent review facility.

      The second study cohort, SEQ-HN, is an observational sub-study and includes 2 types of
      patients: (1) the historical record of first line therapy in AIM-HN (HRAS mutant HNSCC)
      subjects in whom first line outcome data are available and (2) matched control HNSCC patients
      in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide
      first line outcome data and additional follow up.

      HNSCC patients in whom HRAS mutations are identified and who meet eligibility criteria will
      be offered participation in AIM-HN. HNSCC patients in whom HRAS mutations are not identified
      may participate in SEQ-HN only. These patients will be followed and the comparison of
      outcomes of HRAS mutant and HRAS wild type HNSCC will address the exploratory objective to
      determine the effect of HRAS mutation on the ORR of first line systemic therapy in patients
      with recurrent/metastatic HNSCC. Outcome data from subsequent lines of therapy will be
      collected.

Trial Arms

NameTypeDescriptionInterventions
AIM-HNExperimentalTipifarnib, Oral Tablet. Dose Level 1 orally, bid on days 1-7 and 15-21 of 28-day treatment cycles
  • Tipifarnib
SEQ-HNNo InterventionTo obtain historical information of first line therapy in subjects enrolled in AIM-HN, in whom first line outcome data are available and (2) matched control HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.

    Eligibility Criteria

            Inclusion Criteria:

        AIM-HN

          1. At least 18 years of age.

          2. Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx,
             sinonasal, nasopharyngeal, or unknown primary) of squamous histology not amenable to
             local therapy with curative intent (surgery or radiation therapy with or without
             chemotherapy).

          3. Documented tumor progression or recurrence from at least one prior platinum-containing
             regimen in the primary, neoadjuvant, adjuvant, advanced, recurrent or metastatic
             setting.

          4. Known tumor missense HRAS mutation.

          5. Measurable disease by RECIST v1.1.

          6. ECOG performance status of 0-2.

          7. Acceptable liver, renal and hematological function

        Exclusion Criteria:

          1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or
             nonsquamous histologies (e.g. mucosal melanoma).

          2. Received treatment for unstable angina within prior year, myocardial infarction within
             the prior year, cerebro-vascular attack within the prior year, history of New York
             Heart Association grade III or greater congestive heart failure, or current serious
             cardiac arrhythmia requiring medication except atrial fibrillation.

          3. Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological
             symptoms within 4 weeks of Cycle 1 Day 1.

          4. Active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy.
             Known history of infection with human immunodeficiency virus or an active infection
             with hepatitis B or hepatitis C.

          5. Received treatment for non-cancer related liver disease within prior year.

        Inclusion Criteria: SEQ-HN

          1. At least 18 years of age.

          2. Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx,
             sinonasal, nasopharyngeal, or unknown primary) of squamous histology.

          3. Will or has received at least one systemic anti-cancer therapy for recurrent or
             metastatic HNSCC.

        Exclusion Criteria: SEQ-HN

        1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or
        nonsquamous histologies (e.g. mucosal melanoma).
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Objective Response Rate
    Time Frame:2 years
    Safety Issue:
    Description:complete response and partial response

    Secondary Outcome Measures

    Measure:Duration of Response
    Time Frame:2 years
    Safety Issue:
    Description:
    Measure:Time to Response
    Time Frame:2 years
    Safety Issue:
    Description:
    Measure:Progression Free Survival
    Time Frame:2 years
    Safety Issue:
    Description:
    Measure:One year progression free rate
    Time Frame:1 year
    Safety Issue:
    Description:
    Measure:One year survival
    Time Frame:1 year
    Safety Issue:
    Description:
    Measure:overall survival
    Time Frame:2 years
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Kura Oncology, Inc.

    Trial Keywords

    • TIPIFARNIB
    • HEAD AND NECK CANCER

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