E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Asymptomatic or mildly symptomatic chemotherapy-naïve bone predominant metastatic castration-resistant prostate cancer |
Cáncer de próstata resistente a la castración con metástasis predominantemente óseas en pacientes asintomáticos o con síntomas leves que nunca han recibido quimioterapia. |
|
E.1.1.1 | Medical condition in easily understood language |
Patients with prostate cancer with no symptoms or with mild symptoms with metastases mainly in bones, who never had chemotherapy |
Pacientes con cáncer de próstata que no tienen síntomas o éstos son leves, y que nunca han recibido quimioterapia. |
|
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 | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
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 |
The primary objective is to compare the clinical benefit of radium-223 dichloride versus placebo in combination with abiraterone and prednisone/prednisolone in asymptomatic or mildly symptomatic chemotherapynaïve bone predominant metastatic castration-resistant prostate cancer patients. |
El objetivo principal es comparar el beneficio clínico del dicloruro de radio 223 en comparación con placebo en combinación con abiraterona y prednisona/prednisolona en pacientes con cáncer de próstata resistente a la castración con metástasis predominantemente óseas asintomáticos o con síntomas leves que nunca han recibido quimioterapia. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are to compare overal survival, time to opiate use for cancer pain, time to pain progression, time to cytotoxic chemotherapy, radiological progression free survival, acute and long term safety. |
Los objetivos secundarios son comparar la supervivencia global, tiempo hasta el uso de opioides para el dolor neoplásico, tiempo hasta la progresión del dolor, tiempo hasta la quimioterapia citotóxica, supervivencia libre de progresión radiológica, seguridad a corto y largo plazo. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Histologically or cytologically confirmed adenocarcinoma of the prostate
- Male subjects of age > = 18 years
- Prostate cancer progression documented by prostate specific antigen according to the Prostate Cancer Working Group 2 (PCWG2) criteria or radiological progression according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
- Two or more bone metastases on bone scan within 4 weeks prior to randomization with no lung, liver, other visceral and/or brain metastasis.
- Asymptomatic or mildly symptomatic prostate cancer.
- Subjects who received combined androgen blockade with an anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to enrollment.
- Medical or surgical castration with testosterone less than 50 ng/dL (1.7nmol/L).
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 |
- Adenocarcinoma de próstata confirmado histológica o citológicamente
- Pacientes varones > = 18 años de edad
- Progresión del cáncer de próstata confirmada mediante el antígeno prostático específico según los criterios del Grupo 2 de trabajo en el Cáncer de Próstata (PCWG2) o la progresión radiológica según los Criterios de Evaluación de la Respuesta en Tumores Sólidos (RECIST), versión 1.1.
- Dos o más metástasis óseas en la gammagrafía ósea en las 4 semanas previas a la aleatorización, sin metástasis pulmonares, hepáticas o en otras vísceras y/o metástasis cerebrales.
- Cáncer de próstata asintomático o ligeramente sintomático.
- En los pacientes que recibieron bloqueo androgénico combinado con un antiandrógeno se tiene que haber demostrado la progresión del PSA después de suspender el antiandrógeno antes de la inscripción.
- Castración médica o quirúrgica, con testosterona menor de 50 ng/dl (1,7nmol/l).
- Estado funcional de 0 o 1 del Grupo Colaborador de Oncología del Este (ECOG) |
|
E.4 | Principal exclusion criteria |
- Prior cytotoxic chemotherapy for the treatment of CRPC, including taxanes, mitoxantrone and estramustine
- Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone bid.
- Pathological finding consistent with small cell carcinoma of the prostate
- History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations
- History of or known brain metastasis.
- Malignant lymphadenopathy exceeding 3 cm in shortaxis diameter.
- Blood transfusion or erythropoietin stimulating agents prior 4 weeks of screening and during the whole screening period before randomization
- Imminent spinal cord compression based on clinical findings and/or magnetic resonance imaging (MRI). Subjects with history of spinal cord compression should have completely recovered
- Use of opiate analgesics for cancer-related pain, including codeine and dextropropoxyphene, currently or anytime during the 4- week period prior to randomization. |
- Quimioterapia citotóxica previa para el tratamiento del CPRC, incluidos taxanos, mitoxantrona y estramustina
- Cualquier problema médico crónico que requiera una dosis de corticosteroides mayor de 5 mg de prednisona/prednisolona 2 v/d.
- Hallazgos anatomopatológicos compatibles con un carcinoma microcítico de próstata
- Antecedentes de metástasis viscerales o presencia de metástasis viscerales detectadas en las exploraciones radiológicas de selección
- Metástasis cerebrales anteriores o actuales.
- Linfadenopatía maligna mayor de 3 cm de diámetro en su eje menor
- Transfusión de sangre o agentes estimuladores de la eritropoyetina en las 4 semanas previas a la selección y durante todo el período de selección antes de la aleatorización.
- Compresión inminente de la médula espinal según los signos clínicos y/o la resonancia magnética (RM).Los pacientes con antecedentes de compresión de la médula espinal deben haberse recuperado por completo
- Uso de analgésicos opiáceos para el dolor relacionada con el cáncer, incluidos codeína y dextropropoxifeno, en la actualidad o en cualquier momento durante el período de 4 semanas previo a la aleatorización. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Symptomatic skeletal event free survival(SSE-FS) |
Supervivencia sin acontecimientos sintomáticos en los huesos (SSE-FS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
1. Overall Survival
2. Time to opiate use for cancer pain
3. Time to pain progression
4. Time to cytotoxic chemotherapy
5. Radiological progression free survival (rPFS)
6. Number of participants with adverse events as a measure of safety and tolerability |
1. Supervivencia global (SG)
2. El tiempo hasta el uso de opioides para el dolor neoplásico
3. El tiempo hasta la progresión del dolor
4. El tiempo hasta la quimioterapia citotóxica
5. La supervivencia libre de progresión radiológica (rPFS)
6. Número de participantes con acontecimientos adversos como medida de seguridad y tolerabilidad. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At 3 years for interim
At 6 years for final
2. At 3 years
3. At 3 years
4. At 3 years
5. At 3 years
6. Up to 3 years |
1. A los 3 años para los intermedios. A los 6 años para final.
2. A los 3 años
3. A los 3 años
4. A los 3 años
5. A los 3 años
6. Hasta 3 años. |
|
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 | 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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 67 |
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 |
Canada |
China |
France |
Italy |
Japan |
Netherlands |
Norway |
Sweden |
Australia |
Brazil |
Finland |
Germany |
Spain |
Israel |
Poland |
Russian Federation |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
LVLS |
Última visita del último paciente |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |