A research study to find ou whether tipifarnib is safe and effective for the treatment of a type of 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: 18.1Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 18.1Level: PTClassification code 10071971Term: H-ras gene mutationSystem Organ Class: 10018065 - General disorders and administration site conditions
MedDRA version: 18.1Level: 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-ES

Lead Sponsor: Kura Oncology, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 63

Inclusion Criteria

• Histologically or cytologically confirmed diagnosis of non-hematological malignancy for which there is no curative therapy available.
• Tumor that carries a missense HRAS mutation
• Subject consents 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 or radiotherapy regimen prior to enrolment
• ECOG PS 0 or 1
• Acceptable liver function
• Acceptable renal function
• Acceptable hematologic status

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 29
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

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 emerging or rapidly progressing neurological symptoms within 4 weeks first dose. 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 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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<br>disease progression, starting at the end of Cycle 2

Secondary Outcome Measures

Name	Time	Method
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 the 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

Related Trials