Phase II Study of Tipifarnib in non-haematological cancer and HRAS
Research type
Research Study
Full title
An Open Label Phase II Study of Tipifarnib in Advanced Non-Hematological Malignancies with HRAS mutations
IRAS ID
223446
Contact name
Kevin Harrington
Contact email
Sponsor organisation
Kura Oncology
Eudract number
2015-004535-12
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
KO-TIP-001, CTP ID Number; 127,209, US IND Number
Duration of Study in the UK
1 years, 5 months, 25 days
Research summary
Summary of Research
The purpose of this trial is to see how effective an investigational new drug (Tipifarnib, the study drug) is to treat a solid tumour that has not responded to standard treatment. This means that the solid tumour cannot be removed or has returned or is unresponsive to standard treatment.
Tipifarnib is the only drug that will be given to patients who are eligible for this trial. Patients will be allowed to participate in the trial if they meet criteria listed in the study Protocol and will be allocated to one of two groups (cohorts), based the type of cancer that they have.
To be eligible for the trial, patients must have a type of cancer that has a specific genetic mutation (HRAS Mutation) and for which there is no treatment available.
Other reasons for conducting the study are: - To determine for how long Tipifarnib may reduce the size or slow down the growth of the tumour, to determine the side effects of Tipifarnib and to study the tumour and determine why it responds or not to treatment with Tipifarnib.
There are two groups (Cohorts), for the study, of which patients are placed on dependent on disease:-
Cohort 1: Malignant thyroid tumors with HRAS mutations.
Cohort 2: Squamous Head and Neck Cancer with HRAS mutations.Participants must allow for 10 tumour slides (or equivalent tumour tissue block) from previous biopsies, to be sent off for analysis at a central Laboratory.
This is an international trial, with Hospital centres in sites in the US, Europe and Asia. The plan is to have 18 patients of whose data can be reviewed in each study Cohort. Therefore, 36 patients are planned for the study.
Summary of Results
Tipifarnib monotherapy was shown to be well-tolerated with an acceptable safety and tolerability profile at the 600 mg twice a day in alternating weeks schedule. Tipifarnib did not demonstrate antitumor efficacy in subjects with malignant thyroid tumors with HRAS (a gene involved in regulating cell division) mutations. Tipifarnib demonstrated efficacy in subjects with Head and neck squamous cell Carcinoma (HNSCC) with HRAS mutations and in other squamous cell Carcinomas (SCCs) with HRAS mutations and in a subgroup of HNSCC with high HRAS VAF (HRAS gene mutation very frequent in the population). As assessed by the investigator and based on RECIST 1.1, Objective Response Rate (ORR) was 43.5% with 10 subjects achieving partial response (PR) (all HNSCC), 52.6% with 10 subjects achieving PR (HNSCC with high HRAS VAF), and 40.0% (Cohorts 2/Stage 2 and 3 combined, all SCCs) with 12 subjects achieving PR and 48% (all SCCs with high HRAS VAF) with 12 subjects achieving PR. These results indicate that tipifarnib offers a substantial improvement over available therapies currently employed in the second-line or later setting for this population.
REC name
London - South East Research Ethics Committee
REC reference
17/LO/1140
Date of REC Opinion
29 Aug 2017
REC opinion
Further Information Favourable Opinion