Clinical Trials /

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 Thyroid Gland Neoplasm
  • Squamous Cell Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations
  • Official Title: An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies With HRAS Mutations

Clinical Trial IDs

  • ORG STUDY ID: KO-TIP-001
  • NCT ID: NCT02383927

Conditions

  • Thyroid Cancer
  • Squamous Cell Carcinoma Head and Neck Cancer (HNSCC)
  • HRAS Mutant Tumor
  • Other Squamous Cell Carcinoma (SCC) With HRAS Mutant Tumor

Interventions

DrugSynonymsArms
TipifarnibZarnestraCohort 1

Purpose

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

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. Subjects 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 HRAS gene status at a central facility.

      Subjects will be enrolled into three nonrandomized cohorts:

        -  Cohort 1: Malignant thyroid tumors with HRAS mutations (cohort is closed).

        -  Cohort 2: Squamous Cell Carcinoma Head and Neck Cancer with HRAS mutations.

        -  Cohort 3: Squamous Cell Carcinoma (SCC) with HRAS mutations other than HNSCC
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalThyroid Cancer
  • Tipifarnib
Cohort 2ExperimentalSquamous Head and Neck Cancer
  • Tipifarnib

Eligibility Criteria

        Inclusion Criteria:

          -  histologically or cytologically confirmed diagnosis of thyroid cancer (cohort 1: Note:
             Cohort closed to further enrolment) or Squamous Cell Carcinoma head and neck cancer
             (cohort 2) or Squamous Cell Carcinoma other than HNSCC (cohort 3) for which there is
             no curative therapy available.

          -  tumor that carries a missense HRAS mutation ith a variant allele frequency (VAF) >
             20%.

          -  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 • Serum albumin ≥ 3.5 g/dL. Subjects with tumors
             potentially highly sensitive to tipifarnib (HRAS mutant VAF ≥ 35%) may be enrolled
             despite a serum albumin < 3.5 g/dL.

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:24 months (approx. 12 months accrual + 12 months follow up)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Progression-free Survival (PFS)
Time Frame:24 months (approx. 12 months accrual + 12 months follow up)
Safety Issue:
Description:
Measure:Duration of Response (DOR)
Time Frame:24 months (approx. 12 months accrual + 12 months follow up)
Safety Issue:
Description:
Measure:Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame:Until 30 days after the end of study
Safety Issue:
Description:Number of patients that experience Adverse Events (AEs). Adverse Events (AEs) and Serious Adverse Events (SAEs) will be graded according to the NCI-CTCAE (Version 4.03).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Kura Oncology, Inc.

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