E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Non-Hematological Malignancies with HRAS mutations |
Tumores malignos avanzados no hematológicos con mutaciones HRAS |
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E.1.1.1 | Medical condition in easily understood language |
A type of cancer that has a specific genetic mutation and for which there is no curative therapy available |
Un tipo de cancer con una mutación genética específica y para la cual no hay terapia curativa disponible |
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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 | 18.1 |
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) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
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 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
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) |
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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 |
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 |
Determinar la actividad antitumoral en términos de tasa de respuesta objetiva (TR0) de tipifarnib en pacientes con tumores malignos no hematológicos metastásicos, localmente avanzados irresecables, recidivantes y/o refractarios con mutaciones de HRAS. |
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E.2.2 | Secondary objectives of the trial |
Safety and tolerability of tipifarnib in subjects with locally advanced unresectable or metastatic, relapsed and/or refractory, HRAS mutant non hematological malignancies. |
La seguridad y tolerabilidad de tipifarnib en pacientes con tumores malignos no hematológicos metastásicos, localmente avanzados irresecables, recidivantes y/o refractarios con mutaciones de HRAS
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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• Diagnóstico histológico o citológico confirmado de tumor maligno no hematológica para la cual no haya terapia curativa disponible. • Tumor con mutación de HRAS sin sentido • El sujeto proporcionará al menos diez cortes tumorales limpios (o cortes de tejido equivalentes) para la realización de pruebas retrospectivas del estado del tumor del gen HRAS •El sujeto deberá presentar una enfermedad evaluable según los criterios RECIST v.1.1 y recidivante (enfermedad progresiva) o refractaria antes de la terapia. • Al menos 2 semanas desde la última terapia sistémica o radioterapia, antes de ser aleatorizado • ECOG PS 0 o 1 • Aceptable función hepática • Aceptable función renal • Aceptable función hematológica |
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Response assessments according to RECIST 1.1 |
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E.5.1.1 | 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 |
En visita de selección y aproximadamente cada 8 semanas durante los 6 primeros meses ( ciclo 2, 4 y 6) y luego cada 12 semanas ( ciclo 9, 12, 15, etc) hasta progresión de la enfermedad, empezando al finalizar el ciclo 2 |
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E.5.2 | Secondary end point(s) |
Treatment-emergent adverse events (TEAE) and SAEs evaluated according to NCI CTCAE v.4.03 |
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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 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 |
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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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 |
France |
Spain |
United States |
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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
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The end of this clinical study is defined as the day when the last remaining study subject in the trial completes the last Follow-up assessment no later than 12 months after the last study subject is enrolled in the study. Provisions will be made for the continuation of study treatment in patients who demonstrate objective response or disease stabilization and manageable toxicity beyond the end of the study, e.g. a single patient treatment protocol |
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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 9 |