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

NCT ID: NCT02383927

Last Updated: 2024-07-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-13

Study Completion Date

2020-12-14

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1

Thyroid Cancer

Group Type EXPERIMENTAL

Tipifarnib

Intervention Type DRUG

FTase inhibitor

Cohort 2

Squamous Head and Neck Cancer

Group Type EXPERIMENTAL

Tipifarnib

Intervention Type DRUG

FTase inhibitor

Interventions

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Tipifarnib

FTase inhibitor

Intervention Type DRUG

Other Intervention Names

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Zarnestra

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Kura Oncology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of California, Los Angeles

Los Angeles, California, United States

Site Status

Wihship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Oklahoma University Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University Hospital Antwerp

Antwerp, , Belgium

Site Status

Cliniques universitaires Saint-Luc

Brussels, , Belgium

Site Status

CHU

Yvoir, , Belgium

Site Status

Insitut Bergonie

Bordeaux, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Institute Gustave Roussy (IGR)

Paris, , France

Site Status

University Hospital Wuerazburg

Würzburg, , Germany

Site Status

Attikon University Hospital

Attiki, , Greece

Site Status

Instituto Nazionale Tumori

Milan, , Italy

Site Status

University Medical Center

Groningen, , Netherlands

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Hospital Vall d' Hebron

Barcelona, , Spain

Site Status

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status

Hospital del Mar

Barcelona, , Spain

Site Status

Hospital Universitario Doce de Octubre

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

MD Anderson Cancer Center Madrid

Madrid, , Spain

Site Status

START, Centro Integral Oncologico Clara Campal

Madrid, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Complejo Hospitalario de Navarro

Navarro, , Spain

Site Status

Hospital Universitario Virgen de la Rocio

Seville, , Spain

Site Status

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Site Status

Royal Marsden

London, England, United Kingdom

Site Status

University College Hospital

London, England, United Kingdom

Site Status

Countries

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United States Belgium France Germany Greece Italy Netherlands South Korea Spain United Kingdom

References

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Ho AL, Brana I, Haddad R, Bauman J, Bible K, Oosting S, Wong DJ, Ahn MJ, Boni V, Even C, Fayette J, Flor MJ, Harrington K, Kim SB, Licitra L, Nixon I, Saba NF, Hackenberg S, Specenier P, Worden F, Balsara B, Leoni M, Martell B, Scholz C, Gualberto A. Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations. J Clin Oncol. 2021 Jun 10;39(17):1856-1864. doi: 10.1200/JCO.20.02903. Epub 2021 Mar 22.

Reference Type DERIVED
PMID: 33750196 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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KO-TIP-001

Identifier Type: -

Identifier Source: org_study_id

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