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

July 10, 2024 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.

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 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 Léon Bérard
      • 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 Clínic 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 Politecnico 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

Description

Inclusion Criteria:

  • histologically or cytologically confirmed diagnosis of thyroid cancer (cohort 1) 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
Measure Description
Time Frame
Antitumor Activity by Objective Response Rate (ORR)
Time Frame: Up to approximately 3 years

The ORR of tipifarnib was response assessments according to RECIST 1.1. The estimate of the ORR was calculated based on the maximum likelihood estimator (i.e., crude percentage of subjects whose best overall response was complete response [CR] or partial response [PR]). The estimate of the ORR was accompanied by 2-sided 95% confidence interval (CI). The 95% CI was estimated using the Wilson score test-based method.

CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis).

PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.
Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects That Experienced One or More Treatment-emergent Adverse Events (TEAEs)
Time Frame: Up to approximately 3 years
An adverse event (AE) was any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started on or after the first dose of study drug and within 30 days of the last administration of study drug or immediately before the initiation of any other anticancer therapy. The Investigator was required to grade the severity/ intensity of each AE according to NCI-CTCAE version 4.03. If a severity/intensity of Grade 4 (life-threatening) or 5 (death) was applied to an AE, then the Investigator also reported the event as a serious AE.
Up to approximately 3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: Up to approximately 3 years
PFS was defined as the time from first dose (Cycle 1 Day 1) to either first observation of progressive disease (PD) or occurrence of death due to any cause within 126 days (approximately 2 time-intervals for tumour assessments) of either first administration of tipifarnib or the last tumour assessment. Observation of PD could have been by either documented radiographic progression (i.e., scan results) or documentation of symptomatic or clinical progression agreed upon and documented by investigators. In subjects without a progression date or with a death date more than 126 days after the first administration of study drugs or the last tumour assessment, the PFS time should have been censored on the date of last tumour assessment or date of first administration of study tipifarnib.
Up to approximately 3 years
Duration of Response (DOR)
Time Frame: Up to approximately 3 years
DOR was the number of months from start date of PR or CR (whichever response was achieved first) to the first date that PD was documented (in subjects with an objective response). PD was determined by the Investigator using RECIST 1.1. The DOR was right-censored at the date for subjects who achieved CR or PR and met one of the following conditions: 1) when non-protocol anticancer treatment started before documentation of PD, 2) when death prior to documented PD or documented PD after more than 1 missed disease assessment visit, or 3) when alive and did not have documentation of PD before a data analysis cut-off date (therefore, analysis cut-off date was used as the censoring date). Median and 95% CI were calculated via Kaplan-Meier analysis.
Up to approximately 3 years
Overall Survival (OS)
Time Frame: Up to approximately 4 years
An analysis of OS was conducted to estimate median OS time and corresponding 95% CI. OS was defined as the time from first dose (Cycle 1 Day 1) to the occurrence of death due to any cause. In subjects without a death date, the OS was censored on 1) the last date of survival status if alive, 2) a data analysis cut-off date for subjects with no survival status documentation, or 3) the date a subject withdrew consent or was lost to follow-up if there was no additional information. Median and 95% CI were calculated via Kaplan-Meier analysis.
Up to approximately 4 years
Antitumor Activity - Best Overall Response (BOR)
Time Frame: Up to approximately 3 years

BOR according to RECIST 1.1.

Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits.
Up to approximately 3 years

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

May 13, 2015

Primary Completion (Actual)

December 14, 2020

Study Completion (Actual)

December 14, 2020

Study Registration Dates

First Submitted

February 20, 2015

First Submitted That Met QC Criteria

March 3, 2015

First Posted (Estimated)

March 10, 2015

Study Record Updates

Last Update Posted (Actual)

July 11, 2024

Last Update Submitted That Met QC Criteria

July 10, 2024

Last Verified

July 1, 2024

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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