E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic germ cell tumors |
Tumores de células germinativas metastáticos |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic germ cell tumors |
Tumores de células germinativas metastáticos |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 assess the clinical activity of nivolumab monotherapy, as measured by the investigator-assessed CBR, in patients with platinum-recurrent or platinum-refractory metastatic GCT. CBR is defined by sum of CRs, PRs and stable disease (SD) for at least 3 months, with stable or declining tumor markers (αFP and HCG), using Response Evaluation Criteria In Solid Tumors (RECIST 1.1) |
Avaliar a actividade clínica do Nivolumab em monoterapia, medido através da PBC avaliada pelo investigador, em pacientes com TCG metastático recorrente ou refractário à terapêutica com platina. A PBC é definida pela soma das respostas completas, respostas parciais e doença estável com duração superior a 3 meses, utilizando os Critérios de Avaliação de Resposta em Tumores Sólidos (RECIST 1.1), associada a descida ou estabilidade dos marcadores tumorais (αFP e HCG) |
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E.2.2 | Secondary objectives of the trial |
»»Determine CR plus marker-negative PR rate
»»Evaluate overall survival rate (OS)
»»Evaluate Progression Free Survival (PFS)
»»Measure the duration of clinical response |
»»Determinar a Percentagem de Resposta Completa (RC) e Resposta Parcial (RP) com normalização dos marcadores tumorais
»»Analisar a Taxa de Sobrevivência Global (SG)
»»Avaliar a Sobrevivência Livre de Doença (SLD)
»»Medir a duração de resposta clínica |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
»» Male or female, aged 18 years.
»» Metastatic GCT, seminoma or non-seminoma, previously treated with standard doublet or triplet cisplatin-containing chemotherapy for metastatic disease in: a. second or further relapse from primary testicular, retroperitoneal or ovarian GCT; b. first or further relapse of PMNSGCT; c. primary-refractory GCT (defined as progression within 8 weeks of finishing first-line chemotherapy for advanced GCT); or d. “late relapse” (> 2 years after cisplatinum-containing chemotherapy for metastatic GCT) that is not amenable to surgical resection.
»» Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.
»» Evidence of recurrent disease by imaging (CT or MR) or rising tumor markers (αFP or HCG). NOTE: If a rising tumor marker is the only evidence of progressive disease, at least 2 consecutive rising values at least one week apart are needed and alternative causes of increased serum levels of these markers must be excluded (cross reaction with luteinizing hormone (LH) (that can be tested if needed by testosterone suppression of LH), liver disease, use of marijuana, or second primary tumor)
»» Received initial cisplatin based combination therapy, such as BEP, EP, VIP, or similar regimens AND, for primary testicular or ovarian GCT, progression after at least one 'salvage' chemotherapy regimen (such as, TIP, VeIP, VIP or high dose chemotherapy with ASCT). |
»»Doentes com TCG metastático, seminoma ou não-seminoma, previamente tratados com dupleto ou tripleto de quimioterapia standard para doença metastática contendo cisplatina em: a. segunda ou posterior recidiva de TCG primários do testículo, retroperitoneu ou ovário; b. primeira ou posterior recidiva de TCGNSPM; c. TCG refractário (definido pela progressão de doença num período inferior a 8 semanas após término da última linha de quimioterapia para TCG avançado); ou d. “recidiva tardia” (recidiva > 2 anos após quimioterapia para TCG metastático contendo cisplatina) que não é passível de ressecção cirúrgica.
»»Eastern Cooperative Oncology Group (ECOG) performance status de 0 ou 2.
»»Evidência de doença recorrente documentada por exames de imagem (TC ou RM) ou elevação dos marcadores tumorais (αFP or HCG) em doentes com TCG metastático. NOTA: se a elevação dos marcadores tumorais fôr a única evidência de progressão de doença, é necessário pelo menos 2 aumentos consecutivos com pelo menos uma semana de intervalo e excluídas outras etiologias que possam cursar com o aumento destes marcadores (reacção cruzada com hormona luteinizante (LH) (se necessário pode ser confirmada com a supressão de LH com a administração de testosterona), doença hepática, consumo de marijuana, ou um segundo tumor primário).
»»Tratamento prévio com poliquimioterapia contendo cisplatina, como BEP, EP, VIP, ou protocolos semelhantes E, no caso dos TCG do testículo e ovário, progressão tumoral após pelo menos um regime de quimioterapia de recurso (como TIP, VIP ou QTAD) |
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E.4 | Principal exclusion criteria |
»» Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
»» History of allergy or hypersensitivity to study drug components.
»» Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the patient to receive protocol therapy, or interfere with the interpretation of study results.
»» Patients with an active, known or suspected autoimmune disease.
»»»» Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. |
»»Tratamento prévio com anticorpos anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 ou qualquer outro anticorpo ou fármaco dirigido a co-estimuladores de células T ou vias de checkpoint imunitário
»»Antecedentes de alergia ou hipersensibilidade aos componentes do medicamento do estudo.
»»Patologia médica grave ou descontrolada, que na opinião do investigador, possa aumentar o risco de participação no estudo, impedir o doente de receber o medicamento do estudo, ou interferir com a interpretação dos resultados do estudo
»»Doentes com suspeita ou patologia auto-imune conhecida
»»Doentes com antecedentes médicos com necessidade de tratamento sistémica com corticosteroides (>10 mg/dia de prednisolona ou equivalente) ou outra medicação imunossupressora nos 14 dias antes do início da terapêutica com o medicamento do estudo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
clinical benefit rate (CBR) |
Taxa de benefício clínico |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
»»Serum tumor-specific markers every cycle: HCG, αFP and LDH
»»Tumor Imaging Assessment: CT (every 10 weeks) and PET |
»»Marcadores tumorais específicos em cada ciclo:HCG, αFP and LDH
»»Avaliação por Imagem: TC (a cada 10 semanas) e PET |
|
E.5.2 | Secondary end point(s) |
»»Determine CR plus marker-negative PR rate
»»Evaluate overall survival rate (OS)
»»Evaluate Progression Free Survival (PFS)
»»Measure the duration of clinical response |
»»Determinar a Percentagem de Resposta Completa (RC) e Resposta Parcial (RP) com normalização dos marcadores tumorais
»»Analisar a Taxa de Sobrevivência Global (SG)
»»Avaliar a Sobrevivência Livre de Doença (SLD)
»»Medir a duração de resposta clínica |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
»»Serum tumor-specific markers every cycle: HCG, αFP and LDH
»»Tumor Imaging Assessment: CT (every 10 weeks) and PET |
»»Marcadores tumorais específicos em cada ciclo:HCG, αFP and LDH
»»Avaliação por Imagem: TC (a cada 10 semanas) e PET |
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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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |