OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults

Renal Cell Carcinoma Clinical Trial

— OPTI-DOSE  

Official title:

Optimal Dosing of Oral Anticancer Drugs in Older Adults With Cancer: a Randomized Pilot Study.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05949424
• Other study ID #: 16800
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 2024
• Est. completion date: March 2025

Study information

• Verified date: November 2023
• Source: University Medical Center Groningen
• Contact: Esther Broekman, MD
• Phone: +31 50 361 0841
• Email: k.e.broekman[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Carcinoma
• Breast Neoplasms
• Carcinoma
• Carcinoma, Renal Cell
• Endometrial Neoplasms
• Endometrium Carcinoma
• Ovarian Carcinoma
• Renal Cell Carcinoma
• Thyroid Carcinoma
• Thyroid Neoplasms

Intervention

Drug:
• Olaparib
Starting dose of 200mg 2dd.
• Lenvatinib
Starting dose of 10mg 1dd.
• Sunitinib
Starting dose of 25mg 1dd 28/42 days.
• Palbociclib
Starting dose of 75mg 1dd 21/28 days.
• Pazopanib
Starting dose of 200mg 1dd.
• Olaparib
Starting dose of 300mg 2dd.
• Lenvatinib
Starting dose of 20mg 1dd for RCC or endometrial carcinoma, starting dose of 24mg 1dd for thyroid carcinoma.
• Sunitinib
Starting dose of 50mg 1dd 28/42 days.
• Palbociclib
Starting dose of 125mg 1dd 21/28 days.
• Pazopanib
Starting dose of 800mg 1dd.

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of investigating whether a lower starting dose with step-up approach leads to a better overall treatment utility compared to standard dosing	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	12 weeks
Secondary	Overall treatment utility	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	12 weeks
Secondary	Progression free survival	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	up to 60 months
Secondary	Overall survival	From date of randomization until the date of death from any cause, assessed up to 60 months	up to 60 months
Secondary	Quality of life	measured by QLQ-C30 (general) and QLQ-ELD14 (elderly cancer patients)	12 weeks
Secondary	Safety	Adverse events, measured by CTCAE v5.0	12 weeks
Secondary	Hospital care use	number of outpatients visits, telephone contacts or hospital admission days	12 weeks
Secondary	Pharmacokinetic parameters: Cmax	Peak Plasma Concentration (Cmax)	12 weeks
Secondary	Pharmacokinetic parameters: AUC	Area under the plasma concentration versus time curve (AUC)	12 weeks
Secondary	Pharmacokinetic parameters: Ctrough	Trough Plasma Concentration (Ctrough)	12 weeks