E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced non-haematological malignancies with HRAS. |
|
E.1.1.1 | Medical condition in easily understood language |
A type of solid tumour cancer that has a specific genetic mutation and for which there is no curative therapy available |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048683 |
E.1.2 | Term | Advanced cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071971 |
E.1.2 | Term | H-ras gene mutation |
E.1.2 | System Organ Class | 10018065 - General disorders and administration site conditions |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066474 |
E.1.2 | Term | Thyroid cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
A research study to find out whether Tipifarnib is safe and effective for the treatment for advanced tumours with a specific genetic mutation (HRAS) and for which there is no therapy available. |
|
E.2.2 | Secondary objectives of the trial |
**Record how many side effects that may be related to use of Tipifarnib have occurred
**Has Tipifarnib prevented the tumour from growing, by observing the period of Progression Free Survival (PFS) and Duration of Response (DOR)
**Analysis of a small section of the tumour already collected by the patients Oncologist, to help scientists understand if the composition of the tumour, could make it more susceptible to respond to treatment with Tipifarnib |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
**Over 18 yrs
**Histologically or cytologically confirmed diagnosis of non-hematological malignancy for which there is no curative therapy available.
**Tumour that carries a missense HRAS mutation
**Subject consents to provide at least 10 unstained tumour slides (or equivalent tumour tissue blocks) for retrospective testing of HRAS gene tumour 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 heamatologic status
** Female subjects must be either:
a. Of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal)Íž
or
b. Of childbearing potential,must use a highly effective method of contraception, such as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence. Both females and male subjects with female partners of child-bearing potential must agree to use a highly effective method of contraception for 2 weeks prior to screening, during, and at least 4 weeks after last dose of trial medication. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of trial medication. |
|
E.4 | Principal exclusion criteria |
**Ongoing treatment with an anticancer agent
**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
** Subjects who have exhibited allergic reactions to tipifarnib or structural compounds similar to tipifarnib or to the drug product excipients.
** Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective is to determine the antitumour activity in terms of Objective Response Rate of Tipifarnib, in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, HRAS mutant non
haematological malignancies.
Response assessments according to RECIST 1.1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At screening (for a baseline evaluation) 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 end of cycle 2 |
|
E.5.2 | Secondary end point(s) |
Treatment-emergent adverse events (TEAE) and SAEs evaluated according to NCI CTCAE v.4.03 |
|
E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 23 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Greece |
Italy |
Korea, Republic of |
Netherlands |
Spain |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
End of Study occurs no earlier than:
1) 30 days following treatment discontinuation (or until initiation of another anti-cancer therapy) of the last enrolled study subject, or
2) 12 months from enrollment of the last enrolled study subject if sustained clinical benefit is observed (i.e. last enrolled subject continues on study treatment). At that time point, other provisions will be made to transition this
patient to other means of continued treatment with appropriate safety monitoring. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 23 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 25 |