Clinical trial NCT05949424: OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
Official title: Optimal Dosing of Oral Anticancer Drugs in Older Adults With Cancer: a Randomized Pilot Study.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Renal Cell Carcinoma
Ovarian Carcinoma
Thyroid Carcinoma
Breast Carcinoma
Endometrium Carcinoma
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2023-07-18
Enrollment: 30
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Control group: standard SmPC dosing. Intervention group: lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

• 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

Primary outcomes:
measure: Feasibility of investigating whether a lower starting dose with step-up approach leads to a better overall treatment utility compared to standard dosing
timeFrame: 12 weeks
Secondary outcomes:
measure: Overall treatment utility
timeFrame: 12 weeks
measure: Progression free survival
timeFrame: up to 60 months
measure: Overall survival
timeFrame: up to 60 months
measure: Quality of life
timeFrame: 12 weeks
measure: Safety
timeFrame: 12 weeks
measure: Hospital care use
timeFrame: 12 weeks
measure: Pharmacokinetic parameters: Cmax
timeFrame: 12 weeks
measure: Pharmacokinetic parameters: AUC
timeFrame: 12 weeks
measure: Pharmacokinetic parameters: Ctrough
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Esther Broekman, MD
role: PRINCIPAL_INVESTIGATOR
References: