A research study to find out whether Tipifarnib is safe and effective for the treatment of a type of a cancer that has a specific genetic mutation and for which there is no curative therapy available

An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies with HRAS Mutations

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2015-004535-12-BE

Enrollment

Registered

2017-04-21

Start date

2017-10-16

Completion date

Unknown

Last updated

2021-01-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced non-hematological malignancies with HRAS mutations MedDRA version: 20.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10071971 Term: H-ras gene mutation System Organ Class: 10018065 - General disorders and administration site conditions MedDRA version: 20.0 Level: PT Classification code 10066474 Term: Thyroid cancer Syst

Interventions

Product Name: Tipifarnib Product Code: R115777 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: Tipifarnib CAS Number: 192185-72-1 Current Sponsor code: R115777 Other descriptive name: TIP

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: - Subject has a histologically or cytologically confirmed diagnosis of non-hematological malignancy for which there is no curative therapy available: there will be 3 cohorts enrolling patients with more specific localizations of tumors. At this stage, only cohorts 2 and 3 will be open: Subjects must have HNSCC with HRAS mutations in order to be enrolled in the second stage of Cohort 2. Cohort 3 will enroll subjects with SCCs with HRAS mutations other than HNSCC, independently of tissue origin. Subjects with mucosal HNSCC with skin involvement will be enrolled in cohort 2 whereas subjects with primary skin SCC in the head and neck will be enrolled in cohort 3. - tumors that carry a missense HRAS mutation - Subject has consented to provide at least 10 unstained tumor slides (or equivalent tumor tissue blocks) 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 regimen prior to enrolment. - At least 2 weeks since last radiotherapy. - ECOG performance status of 0 or 1 - Acceptable liver function - Acceptable renal function - Acceptable hematologic status - Higly effective method of contraception Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20

Exclusion criteria

Exclusion criteria: - Prior treatment with an FTase inhibitor - Any history of clinically relevant coronary artery disease or myocardial infarction within the last 3 years, New York Heart Association (NYHA) grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or current 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 emerging or rapidly progressing neurological symptoms within 4 weeks of Cycle 1 Day 1. Non-tolerable grade 2 toxicities are defined as those with moderate symptoms that the patient is not able to endure for the conduct of instrumental activities of daily life or that persists = 7 days - Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1, 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.

Design outcomes

Primary

Measure	Time frame
Main Objective: To determine the antitumor activity in terms of ORR of tipifarnib in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, HRAS mutant non hematological malignancies;Secondary Objective: Safety and tolerability of tipifarnib in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, HRAS mutant non hematological malignancies;Primary end point(s): Response assessments according to RECIST 1.1;Timepoint(s) of evaluation of this end point: At screening and approximately every 8 weeks for the first 6 months (cycles 2, 4, 6) and then every 12 weeks (cycles 9, 12, 15, etc..) until disease progression, starting at the end of cycle 2	—

Measure

Time frame

Main Objective: To determine the antitumor activity in terms of ORR of tipifarnib in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, HRAS mutant non hematological malignancies;Secondary Objective: Safety and tolerability of tipifarnib in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, HRAS mutant non hematological malignancies;Primary end point(s): Response assessments according to RECIST 1.1;Timepoint(s) of evaluation of this end point: At screening and approximately every 8 weeks for the first 6 months (cycles 2, 4, 6) and then every 12 weeks (cycles 9, 12, 15, etc..) until disease progression, starting at the end of cycle 2

—

Secondary

Measure	Time frame
Secondary end point(s): Treatment-emergent adverse events (TEAE) and SAEs evaluated according to NCI CTCAE v.4.03;Timepoint(s) of evaluation of this end point: Comprehensive assessment of any apparent toxicity experienced by the subject will be performed throughout the course of the trial (at each study visit and as clinically needed), from the time of subject's signature of informed consent until 30 days from the final administration of the trial treatment or immediately before initiation of any other anticancer therapy, whichever comes first	—

Measure

Time frame

Secondary end point(s): Treatment-emergent adverse events (TEAE) and SAEs evaluated according to NCI CTCAE v.4.03;Timepoint(s) of evaluation of this end point: Comprehensive assessment of any apparent toxicity experienced by the subject will be performed throughout the course of the trial (at each study visit and as clinically needed), from the time of subject's signature of informed consent until 30 days from the final administration of the trial treatment or immediately before initiation of any other anticancer therapy, whichever comes first

—

Countries

Belgium, France, Italy, Netherlands, Spain, United Kingdom, United States

Contacts

Public ContactDirector, Clinical Operations

KURA ONCOLOGY Inc.

karen@kuraoncology.com+1704707.5345

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026