Optimal Dosing of Oral Anticancer Drugs in Older Adults With Cancer: a Randomized Pilot Study.
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Feasibility of investigating whether a lower starting dose with step-up approach leads to a better overall treatment utility compared to standard dosing
研究概览
简要总结
The study hypothesis is that a lower starting dose of anticancer tablet treatments can lead to better treatment tolerability in older patients, while the benefits of treatment can be the same. The trial population consists of 30 patients aged 65 years or older, who are starting treatment with one of these anti cancer tablet treatments: pazopanib, olaparib, lenvatinib, sunitinib or palbociclib. The control group (half of the participants) will be treated with the standard-of-care, the interventional group will start with the lowest dose of the anti cancer tablets as described in the drug label. The dose will be increased every two weeks in case of good tolerability. Results of this pilot study will be used to inform the design of the larger randomised phase 2 trial.
详细描述
Information about the benefits and side effects of treatments for cancer is mainly derived from studies with younger patients. It is known that elderly patients experience more side effects from treatments, which can lead to a worse quality of life. The study hypothesis is that a lower starting dose of anticancer tablet treatments can lead to better treatment tolerability in older patients, while the benefits of treatment can be the same.
The trial population consists of 30 patients aged 65 years or older, who are starting treatment with one of these anti cancer tablet treatments: pazopanib, olaparib, lenvatinib, sunitinib or palbociclib. This is a randomized study with 1:1 randomisation, stratified by type of anti-cancer treatment.
The control group (half of the participants) will be treated with the standard-of-care, that means with the recommended starting dose of the anti cancer tablets as described in the drug label. The dose can be adjusted (lowered) if this is necessary, for example because of side effects, based on the judgment of the treating physician. The interventional group (half of the participants) will start with the lowest dose of the anti cancer tablets as described in the drug label. The dose will be increased every two weeks in case of good tolerability. Results of this pilot study will be used to inform the design of the larger randomised phase 2 trial, for example the primary endpoint, the amount of investigations and the size of the study population.
Study visits are planned every 2 weeks for a total study duration of 12 weeks, the time point for analysis of the primary endpoint. Blood samples for PK analysis are collected every 2 weeks. A baseline blood sample will be collected for pharmacogenomic analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients ≥ 65 years of age.
- •Indication for starting treatment with pazopanib (for renal cell carcinoma), olaparib (for ovarian carcinoma), lenvatinib (as monotherapy for thyroid carcinoma, or in combination with pembrolizumab for renal cell carcinoma or endometrium carcinoma), sunitinib (for renal cell carcinoma) or palbociclib (for breast carcinoma).
- •No contra-indications for starting treatment at the recommended starting dose as per SmPC.
- •All patients must provide written informed consent prior to enrolment.
排除标准
- •Planned starting dose lower than the recommended starting dose as per SmPC
- •For Pazopanib:
- •Use of a strong CYP3A4-inhibitor or PgP-inhibitor
- •Creatinine clearance <30ml/min
- •Moderate or severe hepatic impairment (bilirubin >1.5x ULN)
- •For Olaparib:
- •Use of a moderate or strong CYP3A4-inhibitor
- •Creatinine clearance <50 ml/min
- •Severe hepatic impairment (Child-Pugh 10-15)
- •For Lenvatinib:
- •Creatinine clearance <30ml/min
- •Severe hepatic impairment (Child-Pugh score 10-15)
- •For Sunitinib:
- •Use of a strong CYP3A4-inhibitor
- •Use of a strong CYP3A4-inducer
- •For Palbociclib:
- •Use of a strong CYP3A4-inhibitor
- •Severe hepatic impairment (Child-Pugh score 10-15)
- •Other findings at interview or physical examination that hamper compliance to the study protocol
研究组 & 干预措施
Control group
Standard SmPC dosing with dose adjustments for toxicity as per SmPC
干预措施: Olaparib (Drug)
Control group
Standard SmPC dosing with dose adjustments for toxicity as per SmPC
干预措施: Lenvatinib (Drug)
Control group
Standard SmPC dosing with dose adjustments for toxicity as per SmPC
干预措施: Sunitinib (Drug)
Control group
Standard SmPC dosing with dose adjustments for toxicity as per SmPC
干预措施: Palbociclib (Drug)
Control group
Standard SmPC dosing with dose adjustments for toxicity as per SmPC
干预措施: Pazopanib (Drug)
Intervention group
Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability
干预措施: Olaparib (Drug)
Intervention group
Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability
干预措施: Lenvatinib (Drug)
Intervention group
Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability
干预措施: Sunitinib (Drug)
Intervention group
Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability
干预措施: Palbociclib (Drug)
Intervention group
Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability
干预措施: Pazopanib (Drug)
结局指标
主要结局
Feasibility of investigating whether a lower starting dose with step-up approach leads to a better overall treatment utility compared to standard dosing
时间窗: 12 weeks
* The percentage of patients that are willing to participate, from all eligible patients * The percentage of patients that successfully complete the first 12 weeks of the trial * The percentage of data points that are successfully collected during the first 12 weeks of the trial
次要结局
- Safety(12 weeks)
- Hospital care use(12 weeks)
- Pharmacokinetic parameters: Cmax(12 weeks)
- Pharmacokinetic parameters: AUC(12 weeks)
- Pharmacokinetic parameters: Ctrough(12 weeks)
- Overall treatment utility(12 weeks)
- Progression free survival(up to 60 months)
- Overall survival(up to 60 months)
- Quality of life(12 weeks)