NCT07805122招募中不适用
Intensified Monitoring of PhArmacology of Cabozantinib as a Tool for Toxicity Management in Patients With Renal Cell Carcinoma
适应症
干预措施
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 216
- 试验地点
- 1
- 主要终点
- Impact of the systematic pharmacological counseling activity intervention on Cabozantinib related toxicity
研究概览
简要总结
Adverse events (AEs) with Cabozantinib are frequent (about 40-67% of patients) and often lead to temporary treatment interruptions, dose reductions or permanent discontinuations, potentially reducing dose intensity and sustained exposure. Therefore, strategies are needed to improve tolerability without compromising antitumor activity. Therapeutic drug monitoring (TDM) is particularly suitable for drugs with high interpatient variability, narrow therapeutic windows and defined exposure-response relationships; real world data support this profile for Cabozantinib and suggest that pharmacokinetically guided dosing could help manage toxicity while maintaining efficacy. Based on this evidence, the study proposes a model of individualized pharmacological counselling integrating TDM, pharmacogenetic testing and structured evaluation of pharmacological interactions to optimize Cabozantinib exposure and minimize avoidable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for the intervention group:
- •Patients diagnosed with histologically confirmed advanced/metastatic RCC with predominantly clear cell subtype.
- •Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC, candidate to receive systemic treatment with nivolumab + Cabozantinib or Cabozantinib monotherapy as per clinical practice (investigators choice).
- •Signed Written Informed Consent.
- •Male or female subjects aged ≥18 years old.
- •Women of childbearing potential must avoid pregnancy while on Cabozantinib. Female partners of male patients taking Cabozantinib must also avoid pregnancy. Effective methods of contraception should be used by male and female patients and their partners during therapy, and for at least 4 months after completing therapy. Because oral contraceptives might possibly not be considered as "effective methods of contraception", due to factors such as missed doses, gastrointestinal disturbances, or potential drug interactions that could reduce their effectiveness, they should be used together with another method, such as a barrier method.
- •Previous nephrectomy is permitted.
- •All IMDC (International Metastatic RCC Database Consortium) risk (good, intermediate, poor).
- •Eastern Cooperative Oncology Group performance status 0 or 1
- •Capable of understanding and complying with the protocol requirements.
- •patients will be included in the study regardless of their time of treatment start with Cabozantinib and regardless of their concomitant diseases or co-medication.
排除标准
- •for intervention group:
- •Patients with non-renal cell neoplasms of the kidney (e.g. urothelial, sarcoma, lymphoma).
- •Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of the start of treatment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix or low-grade prostate cancer (≤pT2, N0; Gleason 6) with no plans for treatment intervention.
- •Pregnancy status.
- •Refusal of informed consent.
- •Patients who could not attend periodic clinical check-ups.
- •Any condition that, in the investigator's judgment, could compromise appropriate participation in the study.
- •Inclusion criteria for the historical control group:
- •Patients diagnosed with histologically confirmed advanced/metastatic RCC with predominantly clear cell subtype.
- •Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC, candidate to receive systemic treatment with nivolumab + Cabozantinib or Cabozantinib monotherapy as per clinical practice (investigators choice).
- •Exclusion criteria for the historical control group:
- •Patients with non-renal cell neoplasms of the kidney (e.g. urothelial, sarcoma, lymphoma).
- •Diagnosis of any non-RCC malignancy occurring within 2 years prior to the date of the start of treatment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix or low-grade prostate cancer (≤pT2, N0; Gleason 6) with no plans for treatment intervention.
研究组 & 干预措施
historical control group
No Intervention
interventional group
Experimental
干预措施: Intensified Monitoring of Pharmacology (Other)
结局指标
主要结局
Impact of the systematic pharmacological counseling activity intervention on Cabozantinib related toxicity
时间窗: up to 48 months
The impact will be evaluated as the overall change of the frequency of treatment interruptions due to clinically relevant toxicity in RCC (Renal cell carcinoma) patients treated with Cabozantinib, compared to historical data.
次要结局
- Attitude Towards Pharmacological Counseling Among Oncologists(up to 48 months)
- Validate LC-MS/MS methods for Cabozantinib quantification in plasma and dried blood spot (Capitainer B and Hemaxis) in terms of accuracy(up to 48 months)
- Validate LC-MS/MS methods for Cabozantinib quantification in plasma and dried blood spot (Capitainer B and Hemaxis) in terms of precision(up to 48 months)
- Validate LC-MS/MS methods for Cabozantinib quantification in plasma and dried blood spot (Capitainer B and Hemaxis) in terms of linearity(up to 48 months)
- Explore accuracy of a point-of-care testing (POCT) device for Cabozantinib TDM.(up to 48 months)
- Explore precision of a point-of-care testing (POCT) device for Cabozantinib TDM.(up to 48 months)
- Explore the linearity of a point-of-care testing (POCT) device for Cabozantinib TDM.(up to 48 months)
- Explore comparability of a a point-of-care testing (POCT) device for Cabozantinib TDM with LC-MS method(up to 48 months)
- Characterization of the Exposure-Toxicity Relationship(up to 48 months)
- Assess associations between germline polymorphisms in genes related to Cabozantinib pharmacokinetics and drug exposure levels(up to 48 months)
- Assess associations between germline polymorphisms in genes related to Cabozantinib pharmacokinetics and treatment-related toxicities.(up to 48 months)
- Investigate the association between inflammatory biomarkers (CRP, IL-6, IL-1β, TNF-α, IFN-γ) and Cabozantinib exposure(up to 48 months)
- Investigate the association between inflammatory biomarkers (CRP, IL-6, IL-1β, TNF-α, IFN-γ) and Cabozantinib adverse events.(up to 48 months)
- Measure ctDNA levels via shallow whole-genome sequencing (liquid biopsy) as a tool for monitoring disease response.(up to 48 months)
- Explore molecular biomarker expression patterns in patients starting Cabozantinib therapy for future stratification of toxicity risk.(up to 48 months)
- Assess the feasibility of model-based therapeutic drug monitoring and compare it to the traditional log-linear extrapolation method for estimating Cabozantinib Cmin.(up to 48 months)
- Evaluate influence of covariates (sex, inflammation, genetic polymorphisms) on Cabozantinib PK.(up to 48 months)
- develop a PK/PD model describing the exposure-response and exposure-toxicity relationships for Cabozantinib.(up to 48 months)
研究者
研究点 (1)
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