Clinical trial NCT03719690: Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy
Official title: A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC) With HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HRAS Gene Mutation
HNSCC
Keywords: TIPIFARNIB
HEAD AND NECK CANCER
Lead sponsor: Kura Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2018-10-25
Enrollment: 296
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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
8. Other protocol defined inclusion criteria may apply.

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.
6. Other protocol defined exclusion criteria may apply

Inclusion Criteria: SEQ-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.
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).
5. Other protocol defined inclusion criteria may apply

Exclusion Criteria: SEQ-HN

1. Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).

5. Other protocol defined exclusion criteria may apply

Primary outcomes:
measure: Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF)
timeFrame: Up to approximately 28 months
Secondary outcomes:
measure: ORR in All VAF Population, as Assessed by IRF
timeFrame: Up to approximately 28 months
measure: Duration of Response (DoR) in High VAF Population, as Assessed by IRF
timeFrame: Up to approximately 28 months
measure: DoR in All VAF Population, as Assessed by IRF
timeFrame: Up to approximately 28 months
measure: Progression Free Survival (PFS) in High VAF Population, as Assessed by IRF
timeFrame: Up to approximately 28 months
measure: PFS in All VAF Population, as Assessed by IRF
timeFrame: Up to 28 approximately months
measure: PFS Rate in High VAF Population, as Assessed by IRF
timeFrame: 6 months and 9 months
measure: PFS Rate in All VAF Population, as Assessed by IRF
timeFrame: 6 months and 9 months
measure: Overall Survival (OS) in High VAF Population
timeFrame: Up to approximately 28 months
measure: OS in All VAF Population
timeFrame: Up to approximately 28 months
measure: OS Rate at 12 Months in High VAF Population
timeFrame: 12 months
measure: OS Rate at 12 Months in All VAF Population
timeFrame: 12 months
measure: Time to Response (TTR) in High VAF Population, as Assessed by IRF
timeFrame: Up to approximately 28 months
measure: TTR in All VAF Population, as Assessed by IRF
timeFrame: Up to approximately 28 months
measure: Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 28 months
measure: Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module 35 (EORTC QLQ-H&N35) Subscales
timeFrame: Baseline and End of Treatment Visit (up to approximately 28 months)
measure: Change From Baseline in the EuroQol-Visual Analog Scale (EQ-VAS) Score
timeFrame: Baseline and End of Treatment Visit (up to approximately 28 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA - Jonsson Comprehensive Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF - Helen Diller Family Comprehensive Cancer Center
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope and Innovation - Anaheim
state: California
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Tampa
country: United States
facility: University of South Florida H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Westwood
country: United States
facility: University Of Kansas Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky Markey Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Baltimore
country: United States
facility: Greater Baltimore Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Marlene and Stewart Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Siteman Cancer Center - Washington University Medical Campus
state: Missouri
city: New York
country: United States
facility: New York University Langone Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center-Vanderbilt Ingram Cancer Center
state: Tennessee
city: Fort Sam Houston
country: United States
facility: San Antonio Military Medical Center
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health San Antonio - Mays Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
city: Wien
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien
city: Wien
country: Austria
facility: Hanusch Krankenhaus Wiener Gebietskrankenkasse
city: Yvoir
country: Belgium
facility: Centre Hospitalier Universitaire Universite Catholique de Louvain Site Godinne
state: Namur
city: Antwerpen
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Middelheim
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Mannheim
country: Germany
facility: Universitätsmedizin Mannheim
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg
city: Chaidari
country: Greece
facility: University General Hospital of Athens Attikon
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Thessaloniki
country: Greece
facility: Bioclinic - Thessaloniki
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S. Croce e Carle Cuneo
city: Legnago
country: Italy
facility: Ospedale Mater Salutis di Legnago
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Milano
country: Italy
facility: Fondazione IRCCS - Istituto Nazionale dei Tumori - Milano
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese-L'ospedale Santa Maria alle Scotte
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Jeonju
country: Korea, Republic of
facility: Chonbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea - Seoul St. Mary's Hospital
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea St. Vincent's Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Putrajaya
country: Malaysia
facility: Institut Kanser Negara
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Bergen
country: Norway
facility: Haukeland Universitetssjukehus
city: Oslo
country: Norway
facility: Radiumhospitalet
city: Barcelona
country: Spain
facility: Hospital del Mar - Parc de Salut Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i de Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: HM Centro Integral Oncológico Clara Campal
city: Marbella
country: Spain
facility: Hospital Costa Del Sol
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Santiago De Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Keelung
country: Taiwan
facility: Chang Gung Medical Foundation Keelung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Bangkok
country: Thailand
facility: King Chulalongkorn Memorial Hospital
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital
city: London
country: United Kingdom
facility: Guy's and Saint Thomas' NHS Foundation Trust
state: England
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
Study officials:
References: