Clinical trial NCT02383927: Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations
Official title: An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies With HRAS Mutations
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thyroid Cancer
Squamous Cell Carcinoma Head and Neck Cancer (HNSCC)
HRAS Mutant Tumor
Other Squamous Cell Carcinoma (SCC) With HRAS Mutant Tumor
Lead sponsor: Kura Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2015-03-10
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Phase II study to investigate the antitumor activity in terms of objective response rate (ORR) of tipifarnib in subjects with advanced tumors that carry HRAS mutations and for whom there is no standard curative therapy available.

Detailed description: This Phase II study will investigate the antitumor activity in terms of ORR of tipifarnib in subjects with locally advanced, unresectable or metastatic, relapsed and/or refractory tumors that carry HRAS mutations and for whom there is no curative therapy available. Subjects with information available on tumor HRAS status previously generated are eligible. All subjects must consent to provide at least 10 tumor slides from a prior diagnostic biopsy for a retrospective testing of HRAS gene status at a central facility.

Subjects will be enrolled into three nonrandomized cohorts:

* Cohort 1: Malignant thyroid tumors with HRAS mutations.
* Cohort 2: Squamous Cell Carcinoma Head and Neck Cancer with HRAS mutations.
* Cohort 3: Squamous Cell Carcinoma (SCC) with HRAS mutations other than HNSCC.

Eligibility criteria: Inclusion Criteria:

* histologically or cytologically confirmed diagnosis of thyroid cancer (cohort 1) or Squamous Cell Carcinoma head and neck cancer (cohort 2) or Squamous Cell Carcinoma other than HNSCC (cohort 3) for which there is no curative therapy available.
* tumor that carries a missense HRAS mutation ith a variant allele frequency (VAF) \> 20%.
* Subject consents to provide at least 10 unstained tumor slides for retrospective testing of HRAS gene tumor status
* Subject has measurable disease according to RECIST v1.1 and has relapsed or is refractory to prior therapy.
* At least 2 weeks since the last systemic therapy or radiotherapy regimen prior to enrolment
* ECOG PS 0 or 1
* Acceptable liver function
* Acceptable renal function
* Acceptable hematologic status • Serum albumin ≥ 3.5 g/dL. Subjects with tumors potentially highly sensitive to tipifarnib (HRAS mutant VAF ≥ 35%) may be enrolled despite a serum albumin \< 3.5 g/dL.

Exclusion Criteria:

* Prior treatment with an FTase inhibitor
* History of relevant coronary heart disease or myocardial infarction within last 3 years, NYHA Grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or serious cardiac arrhythmia requiring medication except atrial fibrillation.
* Known uncontrolled brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 4 weeks prior to Cycle 1 Day 1). Controlled brain metastases that require continuous high dose corticosteroid use within 4 weeks of Day 1.
* Non-tolerable \> Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks first dose
* Major surgery, other than diagnostic surgery, within 4 weeks prior to first dose, without complete recovery.
* Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Known infection with HIV, or an active infection with hepatitis B or hepatitis C

Primary outcomes:
measure: Antitumor Activity by Objective Response Rate (ORR)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Number of Subjects That Experienced One or More Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 3 years
Other outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR)
timeFrame: Up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: Up to approximately 4 years
measure: Antitumor Activity - Best Overall Response (BOR)
timeFrame: Up to approximately 3 years
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Atlanta
country: United States
facility: Wihship Cancer Institute of Emory University
state: Georgia
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: Oklahoma University Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
city: Brussels
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Yvoir
country: Belgium
facility: CHU
city: Bordeaux
country: France
facility: Insitut Bergonie
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institute Gustave Roussy (IGR)
city: Würzburg
country: Germany
facility: University Hospital Wuerazburg
city: Attikí
country: Greece
facility: Attikon University Hospital
city: Milan
country: Italy
facility: Instituto Nazionale Tumori
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Groningen
country: Netherlands
facility: University Medical Center
city: Barcelona
country: Spain
facility: Hospital Vall d' Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Madrid
country: Spain
facility: Hospital Universitario Doce de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Madrid
country: Spain
facility: START, Centro Integral Oncologico Clara Campal
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Navarro
country: Spain
facility: Complejo Hospitalario de Navarro
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de la Rocio
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: London
country: United Kingdom
facility: Royal Marsden
state: England
city: London
country: United Kingdom
facility: University College Hospital
state: England
Study officials:
References:
citation: Ho AL, Brana I, Haddad R, Bauman J, Bible K, Oosting S, Wong DJ, Ahn MJ, Boni V, Even C, Fayette J, Flor MJ, Harrington K, Kim SB, Licitra L, Nixon I, Saba NF, Hackenberg S, Specenier P, Worden F, Balsara B, Leoni M, Martell B, Scholz C, Gualberto A. Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations. J Clin Oncol. 2021 Jun 10;39(17):1856-1864. doi: 10.1200/JCO.20.02903. Epub 2021 Mar 22.