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

NCT ID: NCT03719690

Last Updated: 2024-06-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

296 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-15

Study Completion Date

2023-05-02

Brief Summary

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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 including 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

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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 including 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.

Conditions

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HRAS Gene Mutation HNSCC

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AIM-HN

Tipifarnib, Oral Tablet. Dose Level 1 orally, bid on days 1-7 and 15-21 of 28-day treatment cycles

Group Type EXPERIMENTAL

Tipifarnib

Intervention Type DRUG

Tablet for oral administration

HRAS Detection Assay

Intervention Type DEVICE

In Vitro Assay to detect HRAS mutations

SEQ-HN

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Tipifarnib

Tablet for oral administration

Intervention Type DRUG

HRAS Detection Assay

In Vitro Assay to detect HRAS mutations

Intervention Type DEVICE

Eligibility Criteria

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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 treatment failure from most recent prior therapy (e.g. tumor progression, clinical deterioration, or recurrence), and from at least one prior platinum-containing regimen, in any treatment setting.
4. Known tumor missense HRAS mutation.
5. Measurable disease by RECIST v1.1.
6. ECOG performance status of 0-1.
7. Acceptable liver, renal and hematological function


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.
4. HRAS wildtype (i.e., have no identified tumor missense HRAS mutation).

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.


1\. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
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 Southern California Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCLA - Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

UCSF - Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

The Oncology Institute of Hope and Innovation - Anaheim

Whittier, California, United States

Site Status

Miami Cancer Institute

Miami, Florida, United States

Site Status

University of South Florida H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Winship Cancer Institute

Atlanta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University Of Kansas Medical Center

Westwood, Kansas, United States

Site Status

University of Kentucky Markey Cancer Center

Lexington, Kentucky, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Greater Baltimore Medical Center

Baltimore, Maryland, United States

Site Status

Marlene and Stewart Greenebaum Cancer Center

Baltimore, Maryland, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Siteman Cancer Center - Washington University Medical Campus

St Louis, Missouri, United States

Site Status

New York University Langone Medical Center

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt University Medical Center-Vanderbilt Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

San Antonio Military Medical Center

Fort Sam Houston, Texas, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Texas Health San Antonio - Mays Cancer Center

San Antonio, Texas, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

University of Wisconsin

Madison, Wisconsin, United States

Site Status

Peter MacCallum Cancer Centre

Melbourne, , Australia

Site Status

Royal North Shore Hospital

Saint Leonards, , Australia

Site Status

Allgemeines Krankenhaus der Stadt Wien

Vienna, , Austria

Site Status

Hanusch Krankenhaus Wiener Gebietskrankenkasse

Vienna, , Austria

Site Status

Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne

Yvoir, Namur, Belgium

Site Status

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, , Belgium

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status

Universitair Ziekenhuis Leuven

Leuven, , Belgium

Site Status

Rigshospitalet

Copenhagen, , Denmark

Site Status

Herlev Hospital

Herlev, , Denmark

Site Status

Charité Universitätsmedizin Berlin

Berlin, , Germany

Site Status

Universitätsklinikum Leipzig

Leipzig, , Germany

Site Status

Universitätsmedizin Mannheim

Mannheim, , Germany

Site Status

Universitätsklinikum Würzburg

Würzburg, , Germany

Site Status

University General Hospital of Athens Attikon

Chaïdári, , Greece

Site Status

University General Hospital of Larissa

Larissa, , Greece

Site Status

Bioclinic - Thessaloniki

Thessaloniki, , Greece

Site Status

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, , Italy

Site Status

Azienda Ospedaliera S. Croce e Carle Cuneo

Cuneo, , Italy

Site Status

Ospedale Mater Salutis di Legnago

Legnago, , Italy

Site Status

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, , Italy

Site Status

Fondazione IRCCS - Istituto Nazionale dei Tumori - Milano

Milan, , Italy

Site Status

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, , Italy

Site Status

Azienda Ospedaliera Universitaria Senese-L'ospedale Santa Maria alle Scotte

Siena, , Italy

Site Status

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Site Status

Institut Kanser Negara

Putrajaya, , Malaysia

Site Status

Universitair Medisch Centrum Groningen

Groningen, , Netherlands

Site Status

Maastricht University Medical Centre

Maastricht, , Netherlands

Site Status

Universitair Medisch Centrum Utrecht

Utrecht, , Netherlands

Site Status

Haukeland Universitetssjukehus

Bergen, , Norway

Site Status

Radiumhospitalet

Oslo, , Norway

Site Status

National Cancer Center

Goyang-si, , South Korea

Site Status

Chonbuk National University Hospital

Jeonju, , South Korea

Site Status

Korea University Anam Hospital

Seoul, , South Korea

Site Status

Yonsei University Health System Severance Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

The Catholic University of Korea - Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

The Catholic University of Korea St. Vincent's Hospital

Suwon, , South Korea

Site Status

Hospital del Mar - Parc de Salut Mar

Barcelona, , Spain

Site Status

Hospital de la Santa Creu i de Sant Pau

Barcelona, , Spain

Site Status

Hospital Universitari Vall d'Hebrón

Barcelona, , Spain

Site Status

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Site Status

Hospital Duran i Reynals

Barcelona, , Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

HM Centro Integral Oncológico Clara Campal

Madrid, , Spain

Site Status

Hospital Costa Del Sol

Marbella, , Spain

Site Status

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status

Complejo Hospitalario de Navarra

Pamplona, , Spain

Site Status

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Site Status

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Site Status

Changhua Christian Hospital

Changhua, , Taiwan

Site Status

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Chang Gung Medical Foundation Keelung Chang Gung Memorial Hospital

Keelung, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status

Mackay Memorial Hospital

Taipei, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Site Status

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Site Status

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

Site Status

Songklanagarind Hospital

Hat Yai, , Thailand

Site Status

Guy's and Saint Thomas' NHS Foundation Trust

London, England, United Kingdom

Site Status

NHS Greater Glasgow and Clyde

Glasgow, , United Kingdom

Site Status

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

Site Status

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

The Royal Marsden NHS Foundation Trust

Sutton, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Denmark Germany Greece Italy Malaysia Netherlands Norway South Korea Spain Taiwan Thailand United Kingdom

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-007

Identifier Type: -

Identifier Source: org_study_id

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