Um estudo randomizado de fase II comparando a eficácia e a segurança da terapia direcionada ou imunoterapia contra o câncer versus quimioterapia à base de platina em pacientes com câncer de localização primária desconhecida
Patrocinado por: Hoffmann-La Roche
Status de recrutamento
Faixa etária
Sexo
Fase do estudo
Resumo:
Este estudo comparará a eficácia e a segurança da terapia guiada molecularmente versus a quimioterapia padrão contendo platina em participantes com câncer de prognóstico ruim de localização primária desconhecida (CUP; subconjunto não específico) que alcançaram o controle da doença após 3 ciclos de primeira linha quimioterapia de indução à base de platina.
Saiba mais:
Critérios de inclusão:
- Câncer irressecável de sítio primário desconhecido (CUP) histologicamente confirmado, diagnosticado de acordo com os critérios definidos nas Diretrizes de Prática Clínica da European Society for Medical Oncology (ESMO) de 2015 para CUP
- Sem linhas prévias de terapia sistêmica para o tratamento de CUP
- Estado de desempenho do Eastern Cooperative Oncology Group (ECOG) de 0 ou 1
- Candidato a quimioterapia à base de platina (de acordo com a informação de referência para a quimioterapia pretendida)
- Pelo menos uma lesão mensurável de acordo com os Critérios de Avaliação de Resposta em Tumores Sólidos, versão 1.1 (RECIST v1.1)
- Amostra de tecido tumoral fixado em formalina e embebido em parafina (FFPE) = 4 months old that isexpected to be sufficient for generation of a comprehensive genomic profile at acentral reference pathology laboratory
Exclusion Criteria:
- Squamous cell CUP
- Participants who can be assigned to a specific subset of CUP for which a specifictreatment is recommended by the 2015 ESMO Clinical Practice Guidelines for CUP or witha clinical and IHC profile indicative of a specific primary tumor (favorable prognosisCUP subsets): Poorly differentiated carcinoma with midline distribution; women withpapillary adenocarcinoma of the peritoneal cavity; women with adenocarcinoma involvingonly the axillary lymph nodes; squamous cell carcinoma of the cervical lymph nodes;poorly differentiated neuroendocrine tumors; men with blastic bone metastases andelevated prostate-specific antigen (PSA); participants with a single, small,potentially resectable tumor; colon cancer-type CUP, including participants with a CK7negative, CK20 positive, CDX-2 positive immunohistochemistry profile; CK7-positive,CK20-negative and TTF-1 positive tumors in a context suggestive of lung adenocarcinomaor thyroid cancer; IHC profile definitely indicative of breast cancer OR an IHCprofile indicative of breast cancer and either a history of breast cancer or lymphnodes in the drainage areas of the breast; high-grade serious carcinoma histology andelevated CA125 tumor marker and/or a mass in the gynecological tract or any tumor massor lymph node in the abdominal cavity; IHC profile suggestive of renal cell carcinomaand renal lesions, with a Bosniak classification higher than IIF; IHC profilecompatible with cholangiocarcinoma or pancreatobiliary (or upper gastrointestinalcarcinoma) AND 1 or 2 liver lesions without extrahepatic disease or with onlypulmonary metastases and/or lymph nodes in the drainage areas of the liver
- Known presence of brain or spinal cord metastasis (including metastases that have beenirradiated only)
- Histology and immunohistology profiles (per 2015 ESMO guidelines) that are notadenocarcinoma or poorly differentiated carcinoma/adenocarcinoma
- History or known presence of leptomeningeal disease
- Known human immunodeficiency virus (HIV) infection
- Significant cardiovascular disease
- Prior allogeneic stem cell or solid organ transplantation
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatmentor for up to 7 months after the final dose of treatment
Carboplatin
DrogaCarboplatin will be administered intravenously at the area under the curve (AUC) dose once every 3 weeks for up to 9 Cycles (Cycle = 21 days) in some combination with the following: Paclitaxel, Gemcitabine, Atezolizumab, Pertuzumab, and Trastuzumab SC.
Paclitaxel
DrogaPaclitaxel will be administered intravenously, 175 mg/m^2, once every 3 weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Carboplatin, Ipatasertib, Atezolizumab, Pertuzumab, and Trastuzumab SC
Cisplatin
DrogaCisplatin will be administered intravenously, 60-75 mg/m^2, once every three weeks, for up to 9 cycles (Cycle = 21 days) in some combination with the following: Gemcitabine, Paclitaxel, Atezolizumab, Pertuzumab, and Trastuzumab SC.
Gemcitabine
DrogaGemcitabine will be administered intravenously, 1000 mg/m^2, twice every three weeks for up to 9 cycles (Cycle = 21 days) in some combination with the following: Cisplatin, Carboplatin, Atezolizumab, Pertuzumab, and Trastuzumab SC.
Ivosidenib
DrogaIvosidenib will be administered orally at the label-recommended dose (500mg) once daily across a 28-day treatment cycle until loss of clinical benefit or unacceptable toxicity.
Pemigatinib
DrogaPemigatinib will be administered orally at the label-recommended dose (13.5mg) once daily across a 21-day treatment cycle until loss of clinical benefit or unacceptable toxicity.
Olaparib
DrogaOlaparib will be administered orally at the label-recommended dose (400 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Erlotinib
DrogaErlotinib will be administered orally in combination with Bevacizumab at the label recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Bevacizumab
DrogaBevacizumab will be administered intravenously at 15mg/kg every 3 weeks in combination with Erlotinib until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Vemurafenib
DrogaVemurafenib will be administered orally, 960 mg twice daily, in combination with Cobimetinib, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Cobimetinib
DrogaCobimetinib will be administered orally, 60mg once daily, in combination with Vemurafenib, on Days 1-21 of each 28-day Cycle, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Trastuzumab Subcutaneous (SC)
DrogaTrastuzumab will be administered subcutaneously, 600 mg every 3 weeks, in combination with Pertuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Pertuzumab
DrogaPertuzumab will be initially be administered intravenously, 840 mg, followed by 420 mg every 3 weeks, in combination with Trastuzumab and chemotherapy, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months)
Atezolizumab
DrogaAtezolizumab will be administered intravenously at the label-recommended dose (1200 mg), alone or in combination with chemotherapy, every 3 weeks until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Entrectinib
DrogaEntrectinib will be administered orally at the label-recommended dose (600 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Alectinib
DrogaAlectinib will be administered orally at the label-recommended dose (600 mg) twice daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Vismodegib
DrogaVismodegib will be administered orally at the label-recommended dose (150 mg) once daily until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Ipatasertib
DrogaIpatasertib will be administered orally at the label-recommended dose (400 mg) once daily on Days 1-21 of each 28-day Cycle in combination with paclitaxel, and as monotherapy after the final administration of paclitaxel, until loss of clinical benefit or unacceptable toxicity, through the end of the study (approximately 70 months).
Hospital de Câncer de Barretos
Barretos / São Paulo / CEP: 14784-400Instituto do Cancer do Estado de Sao Paulo
São Paulo / São Paulo / CEP: 01246-000Instituto Nacional de Cancer - INCa; Oncologia
Rio de Janeiro / Rio de Janeiro / CEP: 20560-120Hospital Nossa Senhora da Conceicao
Porto Alegre / Rio Grande do Sul / CEP: 91350-200Hospital Sao Rafael - HSR
Salvador / Bahia / CEP: 41253-190Hospital Nossa Senhora da Conceicao
Porto Alegre / RS / CEP: 90040-373As seguintes instituições estão de alguma forma contribuindo com este estudo clínico.
- Foundation Medicine, Inc.
- Código do estudo:
- NCT03498521
- Tipo de estudo:
- Intervencional
- Data de início:
- julho / 2018
- Data de finalização inicial:
- fevereiro / 2023
- Data de finalização estimada:
- junho / 2024
- Número de participantes:
- 528
- Aceita voluntários saudáveis?
- Não