OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
- Conditions
- Thyroid CarcinomaRenal Cell CarcinomaBreast CarcinomaOvarian CarcinomaEndometrium Carcinoma
- Interventions
- Registration Number
- NCT05949424
- Lead Sponsor
- University Medical Center Groningen
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
- 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.
• 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control group Olaparib Standard SmPC dosing with dose adjustments for toxicity as per SmPC Control group Palbociclib Standard SmPC dosing with dose adjustments for toxicity as per SmPC Control group Lenvatinib Standard SmPC dosing with dose adjustments for toxicity as per SmPC Control group Sunitinib Standard SmPC dosing with dose adjustments for toxicity as per SmPC Intervention group Lenvatinib Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability Control group Pazopanib Standard SmPC dosing with dose adjustments for toxicity as per SmPC Intervention group Olaparib Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability Intervention group Sunitinib Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability Intervention group Palbociclib Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability Intervention group Pazopanib Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability
- Primary Outcome Measures
Name Time Method Feasibility of investigating whether a lower starting dose with step-up approach leads to a better overall treatment utility compared to standard dosing 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
- Secondary Outcome Measures
Name Time Method Safety 12 weeks Adverse events, measured by CTCAE v5.0
Hospital care use 12 weeks number of outpatients visits, telephone contacts or hospital admission days
Pharmacokinetic parameters: Cmax 12 weeks Peak Plasma Concentration (Cmax)
Pharmacokinetic parameters: AUC 12 weeks Area under the plasma concentration versus time curve (AUC)
Pharmacokinetic parameters: Ctrough 12 weeks Trough Plasma Concentration (Ctrough)
Overall treatment utility 12 weeks measured by the investigator. See: https://blogs.ed.ac.uk/canceroutcomes/overall-treatment-utility/#:\~:text=In%20Oncology%20clinical%20research%2C%20Overall%20Treatment%20Utility%20%28OTU%29,balance%20of%20benefits%20and%20harms%20from%20cancer%20treatments
Progression free survival up to 60 months From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 60 months
Overall survival up to 60 months From date of randomization until the date of death from any cause, assessed up to 60 months
Quality of life 12 weeks measured by QLQ-C30 (general) and QLQ-ELD14 (elderly cancer patients)
Trial Locations
- Locations (1)
University Medical Center Groningen
🇳🇱Groningen, Netherlands