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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03719690




Registration number
NCT03719690
Ethics application status
Date submitted
16/10/2018
Date registered
25/10/2018
Date last updated
21/06/2024

Titles & IDs
Public title
Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy
Scientific 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)
Secondary ID [1] 0 0
KO-TIP-007
Universal Trial Number (UTN)
Trial acronym
AIM-HN/SEQ-HN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HRAS Gene Mutation 0 0
HNSCC 0 0
Condition category
Condition code
Cancer 0 0 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tipifarnib
Treatment: Devices - HRAS Detection Assay

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

No intervention: 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.


Treatment: Drugs: Tipifarnib
Tablet for oral administration

Treatment: Devices: HRAS Detection Assay
In Vitro Assay to detect HRAS mutations
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF)
Timepoint [1] 0 0
Up to approximately 28 months
Secondary outcome [1] 0 0
ORR in All VAF Population, as Assessed by IRF
Timepoint [1] 0 0
Up to approximately 28 months
Secondary outcome [2] 0 0
Duration of Response (DoR) in High VAF Population, as Assessed by IRF
Timepoint [2] 0 0
Up to approximately 28 months
Secondary outcome [3] 0 0
DoR in All VAF Population, as Assessed by IRF
Timepoint [3] 0 0
Up to approximately 28 months
Secondary outcome [4] 0 0
Progression Free Survival (PFS) in High VAF Population, as Assessed by IRF
Timepoint [4] 0 0
Up to approximately 28 months
Secondary outcome [5] 0 0
PFS in All VAF Population, as Assessed by IRF
Timepoint [5] 0 0
Up to 28 approximately months
Secondary outcome [6] 0 0
PFS Rate in High VAF Population, as Assessed by IRF
Timepoint [6] 0 0
6 months and 9 months
Secondary outcome [7] 0 0
PFS Rate in All VAF Population, as Assessed by IRF
Timepoint [7] 0 0
6 months and 9 months
Secondary outcome [8] 0 0
Overall Survival (OS) in High VAF Population
Timepoint [8] 0 0
Up to approximately 28 months
Secondary outcome [9] 0 0
OS in All VAF Population
Timepoint [9] 0 0
Up to approximately 28 months
Secondary outcome [10] 0 0
OS Rate at 12 Months in High VAF Population
Timepoint [10] 0 0
12 months
Secondary outcome [11] 0 0
OS Rate at 12 Months in All VAF Population
Timepoint [11] 0 0
12 months
Secondary outcome [12] 0 0
Time to Response (TTR) in High VAF Population, as Assessed by IRF
Timepoint [12] 0 0
Up to approximately 28 months
Secondary outcome [13] 0 0
TTR in All VAF Population, as Assessed by IRF
Timepoint [13] 0 0
Up to approximately 28 months
Secondary outcome [14] 0 0
Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)
Timepoint [14] 0 0
Up to approximately 28 months
Secondary outcome [15] 0 0
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
Timepoint [15] 0 0
Baseline and End of Treatment Visit (up to approximately 28 months)
Secondary outcome [16] 0 0
Change From Baseline in the EuroQol-Visual Analog Scale (EQ-VAS) Score
Timepoint [16] 0 0
Baseline and End of Treatment Visit (up to approximately 28 months)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/03/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
2/05/2023
Sample size
Target
Accrual to date
Final
296
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
2065 - Saint Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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State/province [2] 0 0
Florida
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Georgia
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Illinois
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Kansas
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Kentucky
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Missouri
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New York
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North Carolina
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Ohio
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Oklahoma
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Pennsylvania
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Tennessee
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Texas
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Washington
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Wisconsin
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Austria
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Wien
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Belgium
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Namur
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Belgium
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Antwerpen
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Belgium
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Brussels
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Edegem
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Leuven
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Copenhagen
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Herlev
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Leipzig
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Mannheim
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Chaidari
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Larissa
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Siena
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Jeonju
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Suwon
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Malaysia
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Kuala Lumpur
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Malaysia
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Putrajaya
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Groningen
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Maastricht
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Utrecht
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Bergen
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Oslo
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Barcelona
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Madrid
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Marbella
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Málaga
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Pamplona
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Santiago De Compostela
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Sevilla
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Valencia
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Zaragoza
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Taiwan
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Changhua
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Keelung
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Taichung
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Tainan
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Taipei
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Taoyuan
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Thailand
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Bangkok
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Thailand
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Chiang Mai
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Thailand
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Hat Yai
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United Kingdom
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England
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Glasgow
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London
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Manchester
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United Kingdom
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Kura Oncology, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT03719690
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03719690