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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03719690




Registration number
NCT03719690
Ethics application status
Date submitted
16/10/2018
Date registered
25/10/2018
Date last updated
9/11/2022

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 in High Variable Allele Frequency (VAF) population
Timepoint [1] 0 0
2 years
Secondary outcome [1] 0 0
Objective Response Rate in any VAF population
Timepoint [1] 0 0
2 years
Secondary outcome [2] 0 0
Duration of Response in High VAF population
Timepoint [2] 0 0
2 years
Secondary outcome [3] 0 0
Duration of Response in any VAF population
Timepoint [3] 0 0
2 years
Secondary outcome [4] 0 0
Progression Free Survival in both high VAF and all VAF populations
Timepoint [4] 0 0
6 and 9 months
Secondary outcome [5] 0 0
Overall survival in both high VAF and all VAF populations
Timepoint [5] 0 0
1 year
Secondary outcome [6] 0 0
Overall survival in both high VAF and all VAF populations
Timepoint [6] 0 0
2 years
Secondary outcome [7] 0 0
Investigate safety and tolerability of tipifarnib according to NCI CTCAE v5.0
Timepoint [7] 0 0
30 days after treatment discontinuation
Secondary outcome [8] 0 0
Time to Response in both high VAF and all VAF populations
Timepoint [8] 0 0
2 years
Secondary outcome [9] 0 0
Time to Progression in both high VAF and all VAF populations
Timepoint [9] 0 0
2 years
Secondary outcome [10] 0 0
Investigate effects of tipifarnib treatment on quality of life using EORTC QLQ-H&N35
Timepoint [10] 0 0
2 years
Secondary outcome [11] 0 0
Evaluate the concentration of tipifarnib [pharmacokinetics (PK)] in blood samples over time
Timepoint [11] 0 0
6 months
Secondary outcome [12] 0 0
Investigate effects of tipifarnib treatment on quality of life using EQ-5D-5L
Timepoint [12] 0 0
2 years

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/11/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/05/2023
Actual
Sample size
Target
284
Accrual to date
Final
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
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United States of America
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California
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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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Wien
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Namur
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Edegem
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Bergen
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Marbella
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Valencia
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Chiang Mai
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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/ct2/show/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
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Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03719690