E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
any type of solid tumor metastatic melanoma |
Cualquier tìpo de tumor sólido Melanoma metastásico |
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E.1.1.1 | Medical condition in easily understood language |
patients with BRAFV600 mutation-positive cancer (including metast. melanoma or other cancer types), without acceptable standard treatment options |
Pacientes positivos para la mutación BRAFV600 (melanoma metastásico u otro tipo de cáncer) previamente incluidos en un protocolo anterior de vemurafenib |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025670 |
E.1.2 | Term | Malignant melanoma stage III |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025669 |
E.1.2 | Term | Malignant melanoma stage II |
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 provide continued access to vemurafenib for eligible patients with BRAFV600 mutation-positive malignancy who were previously treated for an antecedent vemurafenib protocol without meetings its definite criteria for disease progression there and may potentially benefit from continued treatment with vemurafenib |
El objetivo principal de este estudio es proporcionar acceso continuo a vemurafenib a pacientes elegibles con neoplasia maligna con la mutación BRAFV600 que recibieron tratamiento previo en un protocolo anterior de vemurafenib y no cumplieron los criterios del protocolo de progresión de la enfermedad, o están recibiendo tratamiento después de la progresión y siguen obteniendo beneficio clínico, según la evaluación del investigador, y posiblemente puedan beneficiarse del tratamiento continuado con vemurafenib. |
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E.2.2 | Secondary objectives of the trial |
To collect and describe ongoing/continuing safety and tolerability data for patients entering the extension (rollover), once all necessary information for the antecedent study has been collected |
El objetivo secundario es recopilar y describir los datos de seguridad y tolerabilidad de los pacientes que continúan el tratamiento con vemurafenib en este estudio de extensión (transferencia). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Disease-Specific Inclusion Criteria: - BRAFV600 mutation positive malignancy - Prior eligibility and treatment in an antecedent vemurafenib protocol - Ability to begin treatment in the extension (rollover) protocol within 15 days following the last day of study in the antecedent protocol General Inclusion Criteria: - Signed informed consent form(s) - Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two adequate methods of contraception including at least one method with a failure rate of < 1% per year during the course of this study and for at least 6 months after completion of study treatment. - Females of childbearing potential are defined as sexually mature women without prior hysterectomy who have had any evidence of menses in the past 12 months. In order to be considered NOT of childbearing potential, amenorrhea for a period of 12 months or longer must have occurred in the absence of chemotherapy, anti estrogen therapy, or ovarian suppression. - Effective forms of contraception include surgical sterilization, a reliable barrier method with spermicide, birth control pills, contraceptive hormone implants, or vasectomized partner. - Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential; women of non-childbearing potential may be included if they are either surgically sterile or have been naturally menopausal for ? 1 year. Women of non childbearing potential need not undergo the pregnancy test. |
Criterios de inclusión específicos de la enfermedad: 1.Neoplasia maligna positiva para la mutación BRAFV600. 2.Elegibilidad previa para un protocolo anterior con vemurafenib y que hayan recibido el tratamiento del estudio. 3.Capacidad para iniciar el tratamiento del protocolo de extensión (transferencia) en un plazo de 15 días desde el último día del estudio del protocolo anterior. Criterios de inclusión generales: 1.Documento(s) de consentimiento informado firmados. 2.Las pacientes en edad fértil y los pacientes con parejas en edad fértil deberán acceder a utilizar siempre dos métodos anticonceptivos adecuados, incluyendo al menos 1 método con una tasa de fracaso < 1% al año durante todo este estudio y durante al menos 6 meses después de finalizar el tratamiento del estudio. ?Entre los métodos anticonceptivos eficaces se incluyen la esterilización quirúrgica, un método de barrera fiable con espermicida, píldoras anticonceptivas, implantes hormonales anticonceptivos o pareja vasectomizada. 3.Resultado negativo de la prueba de embarazo en suero en los 7 días previos al inicio de la administración en mujeres en edad fértil; podrá incluirse a mujeres que no estén en edad fértil si se han sometido a esterilización quirúrgica o han tenido una menopausia natural durante < 1 año. Las mujeres que no estén en edad fértil no necesitan someterse a la prueba de embarazo. |
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E.4 | Principal exclusion criteria |
- Adverse event requiring discontinuation of vemurafenib in the antecedent protocol - Progressive disease during the antecedent protocol. If approval to treat beyond progression was already given in the antecedent protocol, the patient may roll over into the current protocol without sponsor approval. Under special circumstances, when it is felt that the patient may clinically benefit by continued therapy with vemurafenib, enrollment into this protocol and dosing beyond progression may considered, if it is judged by the investigator, in consultation with the Sponsor, to be in the best interest of the patient. All such cases will require approval of the Sponsor before enrolling the patient into this protocol. - Meeting any of the following exclusion criteria of the antecedent study at the time the patient is considered for the extension (rollover) study: - Current, recent (within 28 days prior to Day 1), or planned use of any antitumor therapy outside of this study - Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient?s ability to participate in the study - History of malabsorption or other clinically significant metabolic dysfunction - History of clinically significant cardiac or pulmonary dysfunction as specified in antecedent study |
1.Acontecimiento adverso que requiriera la interrupción de vemurafenib en el protocolo anterior. 2.Progresión de la enfermedad durante el protocolo anterior. En caso de que durante el protocolo anterior se acordara mantener el tratamiento después de la progresión, el paciente podrá participar en el presente protocolo sin la aprobación del promotor. En determinadas circunstancias, cuando se considere que el paciente puede obtener beneficio clínico del tratamiento continuado con vemurafenib, podrá considerarse su inclusión en este protocolo y la administración de la dosis posterior a la progresión, si el investigador considera, tras consultarlo con el promotor, que es lo mejor para el paciente. Todos estos casos precisarán la aprobación del promotor antes de la inclusión del paciente en este protocolo. 3.El cumplimiento de cualquiera de los siguientes criterios de exclusión del estudio anterior en el momento en que se considera al paciente para el estudio de extensión (transferencia): ?Uso actual, reciente (en los 28 días previos al día 1) o previsto de cualquier tratamiento antineoplásico ajeno al estudio. ?Cualquier otra enfermedad concomitante grave que, en opinión del investigador, comprometería la seguridad del paciente o su capacidad para participar en el estudio. ?Antecedentes de malabsorción u otra disfunción metabólica clínicamente significativa. ?Antecedentes de disfunción pulmonar o cardíaca clínicamente significativa según lo especificado en el estudio anterior. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To provide continued access to vemurafenib for eligible patients with BRAFV600 mutation-positive malignancy who were previously treated in an antecedent vemurafenib protocol and did not meet the protocol?s criteria for disease progression, or are being treated beyond progression and are still deriving clinical benefit, as assessed by investigator and may potentially benefit from continued treatment with vemurafenib |
El objetivo principal de este estudio es proporcionar acceso continuado a vemurafenib a pacientes elegibles con neoplasia maligna con la mutación BRAFV600 que recibieron tratamiento previo en un protocolo anterior de vemurafenib y no cumplieron los criterios del protocolo de progresión de la enfermedad, o están recibiendo tratamiento después de la progresión y siguen obteniendo beneficio clínico, según la evaluación del investigador, y posiblemente puedan beneficiarse del tratamiento continuo con vemurafenib. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To collect and describe safety and tolerability data for patients who continue vemurafenib treatment in this extension (rollover) study |
recopilar y describir los datos de seguridad y tolerabilidad de los pacientes que continúan el tratamiento con vemurafenib en este estudio de extensión (transferencia). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Continuous during treatment (monthly visit for the first 7 months, bi-monthly therafter) and 3 and 6 months after treatment discontinuation |
Meses continuos durante el tratamiento (visita mensual durante los primeros 7 meses, cada dos meses a partir de entonces) y 3 y 6 después de la interrupción del tratamiento |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
continuous access to vemurafenib for eligible patients in treatment need (see primary objective above) |
acceso continuo a vemurafenib para los pacientes elegibles que necesitan tratamiento (véase el objetivo principal de arriba) |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Argentina |
Australia |
Belarus |
Belgium |
Bosnia and Herzegovina |
Brazil |
Canada |
Croatia |
Cyprus |
Egypt |
Finland |
Germany |
Greece |
Hungary |
Israel |
Korea, Republic of |
Netherlands |
New Zealand |
Peru |
Portugal |
Romania |
Russian Federation |
Serbia |
South Africa |
Spain |
Switzerland |
Turkey |
United Kingdom |
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
|
All patients will be followed for SCC (cutaneous and non-cutaneous), according to the RMP, for up to 6 months after their last dose of vemurafenib or until the Sponsor decides to end the trial, whichever occurs first. |
Se realizará un seguimiento de todos los pacientes para la detección de CCE (cutáneo o no), de conformidad con el PGR, durante un máximo de 6 meses después de la última dosis de vemurafenib o hasta que el promotor decida poner fin al ensayo, lo que suceda primero. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 60 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 60 |