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

May 12, 2021 updated by: Kura Oncology, Inc.

An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies With HRAS Mutations

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Antwerp, Belgium
        • University Hospital Antwerp
      • Brussels, Belgium
        • Cliniques Universitaires Saint-Luc
      • Yvoir, Belgium
        • CHU
  • France
      • Bordeaux, France
        • Insitut Bergonié
      • Lyon, France
        • Centre Leon Berard
      • Nice, France
        • Centre Antoine Lacassagne
      • Paris, France
        • Institute Gustave Roussy (Igr)
  • Germany
      • Würzburg, Germany
        • University Hospital Wuerazburg
  • Greece
      • Attikí, Greece
        • Attikon University Hospital
  • Italy
      • Milan, Italy
        • Instituto Nazionale Tumori
  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Asan Medical Center
      • Seoul, Korea, Republic of
        • Samsung Medical Center
  • Netherlands
      • Groningen, Netherlands
        • University Medical Center
  • Spain
      • Barcelona, Spain
        • Hospital Clinic de Barcelona
      • Barcelona, Spain
        • Hospital del Mar
      • Barcelona, Spain, 08035
        • Hospital Vall d' Hebron
      • Madrid, Spain
        • MD Anderson Cancer Center Madrid
      • Madrid, Spain
        • Hospital Universitario La Paz
      • Madrid, Spain
        • Hospital Universitario Doce de Octubre
      • Madrid, Spain
        • START, Centro Integral Oncologico Clara Campal
      • Málaga, Spain
        • Hospital Universitario Virgen de la Victoria
      • Navarro, Spain
        • Complejo Hospitalario de Navarro
      • Sevilla, Spain
        • Hospital Universitario Virgen de la Rocio
      • Valencia, Spain
        • Hospital Universitario y Politécnico La Fe
  • United Kingdom
    • England
      • London, England, United Kingdom
        • Royal Marsden
      • London, England, United Kingdom
        • University College Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90404
        • University of California, Los Angeles
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Wihship Cancer Institute of Emory University
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Comprehensive Cancer Center
    • Minnesota
      • Rochester, Minnesota, United States, 55902
        • Mayo Clinic
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan-Kettering Cancer Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Health Sciences Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas Md Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1
Thyroid Cancer
Drug: Tipifarnib
FTase inhibitor
Other Names:
  • Zarnestra
Experimental: Cohort 2
Squamous Head and Neck Cancer
Drug: Tipifarnib
FTase inhibitor
Other Names:
  • Zarnestra

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: 24 months (approx. 12 months accrual + 12 months follow up)
24 months (approx. 12 months accrual + 12 months follow up)
Duration of Response (DOR)
Time Frame: 24 months (approx. 12 months accrual + 12 months follow up)
24 months (approx. 12 months accrual + 12 months follow up)
Number of Subjects with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Until 30 days after the end of study
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).
Until 30 days after the end of study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kura Oncology, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2015

Primary Completion (Actual)

November 30, 2020

Study Completion (Actual)

November 30, 2020

Study Registration Dates

First Submitted

February 20, 2015

First Submitted That Met QC Criteria

March 3, 2015

First Posted (Estimate)

March 10, 2015

Study Record Updates

Last Update Posted (Actual)

May 14, 2021

Last Update Submitted That Met QC Criteria

May 12, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KO-TIP-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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