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

Phase 1

• Conditions: Advanced non-hematological malignancies with HRAS mutations; MedDRA version: 20.0Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10071971Term: H-ras gene mutationSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 20.0Level: PTClassification code 10066474Term: Thyroid cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-004535-12-BE
• Lead Sponsor: KURA ONCOLOGY Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-04-21
• Last Update Posted: 5 January 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 62

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

- 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified