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

NCT03719690 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: KO-TIP-007
• Study Type: interventional
• Target: 296
• Locations: 15 countries
• Sites: 100

Brief Summary

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.

Conditions

HRAS Gene Mutation; HNSCC

Keywords

TIPIFARNIB; HEAD AND NECK CANCER

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF)

  ORR was defined as the percentage of participants who experienced a best overall response (BOR) of complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by IRF. 95% confidence interval (CI) was calculated by the exact binomial (Clopper-Pearson) method.

  Up to approximately 28 months

Secondary Outcomes (16)

• ORR in All VAF Population, as Assessed by IRF

  Up to approximately 28 months

• Duration of Response (DoR) in High VAF Population, as Assessed by IRF

  Up to approximately 28 months

• DoR in All VAF Population, as Assessed by IRF

  Up to approximately 28 months

• Progression Free Survival (PFS) in High VAF Population, as Assessed by IRF

  Up to approximately 28 months

• PFS in All VAF Population, as Assessed by IRF

  Up to 28 approximately months

Study Arms (2)

AIM-HN

EXPERIMENTAL

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

Drug: Tipifarnib; Device: HRAS Detection Assay

SEQ-HN

NO INTERVENTION

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.

Interventions

Tipifarnib DRUG

Tablet for oral administration

AIM-HN

HRAS Detection Assay DEVICE

In Vitro Assay to detect HRAS mutations

AIM-HN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• AIM-HN
• At least 18 years of age.
• 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).
• 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.
• Known tumor missense HRAS mutation.
• Measurable disease by RECIST v1.1.
• ECOG performance status of 0-1.
• Acceptable liver, renal and hematological function

You may not qualify if:

• Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
• 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.
• Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
• 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.
• Received treatment for non-cancer related liver disease within prior year.
• At least 18 years of age.
• Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology.
• Will or has received at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC.
• HRAS wildtype (i.e., have no identified tumor missense HRAS mutation).
• \. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).

Sponsors & Collaborators

• Kura Oncology, Inc.: lead

Study Sites (102)

University of Southern California Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA - Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

UCSF - Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

Location

The Oncology Institute of Hope and Innovation - Anaheim

Whittier, California, 90603, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

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

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University Of Kansas Medical Center

Westwood, Kansas, 66205, United States

Location

University of Kentucky Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Greater Baltimore Medical Center

Baltimore, Maryland, 21204, United States

Location

Marlene and Stewart Greenebaum Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Siteman Cancer Center - Washington University Medical Campus

St Louis, Missouri, 63129, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Vanderbilt University Medical Center-Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

San Antonio Military Medical Center

Fort Sam Houston, Texas, 78234, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Texas Health San Antonio - Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

Peter MacCallum Cancer Centre

Melbourne, 3000, Australia

Location

Royal North Shore Hospital

Saint Leonards, 2065, Australia

Location

Allgemeines Krankenhaus der Stadt Wien

Vienna, 1090, Austria

Location

Hanusch Krankenhaus Wiener Gebietskrankenkasse

Vienna, 1140, Austria

Location

Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne

Yvoir, Namur, 5530, Belgium

Location

Ziekenhuis Netwerk Antwerpen Middelheim

Antwerp, 2020, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Herlev Hospital

Herlev, 2730, Denmark

Location

Charité Universitätsmedizin Berlin

Berlin, 12203, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitätsmedizin Mannheim

Mannheim, 68167, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

University General Hospital of Athens Attikon

Chaïdári, 12462, Greece

Location

University General Hospital of Larissa

Larissa, 41110, Greece

Location

Bioclinic - Thessaloniki

Thessaloniki, 54622, Greece

Location

Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi

Bologna, 40138, Italy

Location

Azienda Ospedaliera S. Croce e Carle Cuneo

Cuneo, 12100, Italy

Location

Ospedale Mater Salutis di Legnago

Legnago, 37045, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

Fondazione IRCCS - Istituto Nazionale dei Tumori - Milano

Milan, 20133, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale

Napoli, 80131, Italy

Location

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

Siena, 53100, Italy

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Institut Kanser Negara

Putrajaya, 62250, Malaysia

Location

Universitair Medisch Centrum Groningen

Groningen, 9713 GZ, Netherlands

Location

Maastricht University Medical Centre

Maastricht, 6229 HX, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Haukeland Universitetssjukehus

Bergen, 1521, Norway

Location

Radiumhospitalet

Oslo, 0379, Norway

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Chonbuk National University Hospital

Jeonju, 54907, South Korea

Location

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

Yonsei University Health System Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

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

Seoul, 06591, South Korea

Location

The Catholic University of Korea St. Vincent's Hospital

Suwon, 16247, South Korea

Location

Hospital del Mar - Parc de Salut Mar

Barcelona, 08003, Spain

Location

Hospital de la Santa Creu i de Sant Pau

Barcelona, 08025, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

HM Centro Integral Oncológico Clara Campal

Madrid, 28050, Spain

Location

Hospital Costa Del Sol

Marbella, 29603, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, 31008, Spain

Location

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, 15707, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

Chang Gung Medical Foundation Keelung Chang Gung Memorial Hospital

Keelung, 20442, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

Mackay Memorial Hospital

Taipei, 10099, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan District, 33305, Taiwan

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, 50200, Thailand

Location

Songklanagarind Hospital

Hat Yai, 90110, Thailand

Location

Guy's and Saint Thomas' NHS Foundation Trust

London, England, SE1 9RT, United Kingdom

Location

NHS Greater Glasgow and Clyde

Glasgow, G12 0XH, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2BU, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Results Point of Contact

• Title: Clinical Operations
• Organization: Kura Oncology, Inc.

KO-TIP-007@kuraoncology.com

617-588-3755

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: October 25, 2018
• Study Start: March 15, 2019
• Primary Completion: May 2, 2023
• Study Completion: May 2, 2023
• Last Updated: June 21, 2024
• Results First Posted: June 21, 2024

Record last verified: 2024-05

Locations

GR (3); BE (5); IT (7); TH (3); US (29); ES (15); TW (9); AU (2); DK (2); MY (2); KR (8); DE (4); NO (2); NL (3); GB (6)