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

November 28, 2023 updated by: University Medical Center Groningen

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

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • University Medical Center Groningen
        • Contact:
        • Principal Investigator:
          • Esther Broekman, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control group
Standard SmPC dosing with dose adjustments for toxicity as per SmPC
Drug: Olaparib
Starting dose of 200mg 2dd.
Other Names:
  • Lynparza
Drug: Lenvatinib
Starting dose of 10mg 1dd.
Other Names:
  • Lenvima
Drug: Sunitinib
Starting dose of 25mg 1dd 28/42 days.
Other Names:
  • Sutent
Drug: Palbociclib
Starting dose of 75mg 1dd 21/28 days.
Other Names:
  • Ibrance
Drug: Pazopanib
Starting dose of 200mg 1dd.
Other Names:
  • Votrient
Drug: Olaparib
Starting dose of 300mg 2dd.
Other Names:
  • Lynparza
Drug: Lenvatinib
Starting dose of 20mg 1dd for RCC or endometrial carcinoma, starting dose of 24mg 1dd for thyroid carcinoma.
Other Names:
  • Lenvima
Drug: Sunitinib
Starting dose of 50mg 1dd 28/42 days.
Other Names:
  • Sutent
Drug: Palbociclib
Starting dose of 125mg 1dd 21/28 days.
Other Names:
  • Ibrance
Drug: Pazopanib
Starting dose of 800mg 1dd.
Other Names:
  • Votrient
Experimental: Intervention group
Lower starting dose with dose-escalation inversely following the dosing steps from the SmPC every 2 weeks in case of good tolerability
Drug: Olaparib
Starting dose of 200mg 2dd.
Other Names:
  • Lynparza
Drug: Lenvatinib
Starting dose of 10mg 1dd.
Other Names:
  • Lenvima
Drug: Sunitinib
Starting dose of 25mg 1dd 28/42 days.
Other Names:
  • Sutent
Drug: Palbociclib
Starting dose of 75mg 1dd 21/28 days.
Other Names:
  • Ibrance
Drug: Pazopanib
Starting dose of 200mg 1dd.
Other Names:
  • Votrient
Drug: Olaparib
Starting dose of 300mg 2dd.
Other Names:
  • Lynparza
Drug: Lenvatinib
Starting dose of 20mg 1dd for RCC or endometrial carcinoma, starting dose of 24mg 1dd for thyroid carcinoma.
Other Names:
  • Lenvima
Drug: Sunitinib
Starting dose of 50mg 1dd 28/42 days.
Other Names:
  • Sutent
Drug: Palbociclib
Starting dose of 125mg 1dd 21/28 days.
Other Names:
  • Ibrance
Drug: Pazopanib
Starting dose of 800mg 1dd.
Other Names:
  • Votrient

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility of investigating whether a lower starting dose with step-up approach leads to a better overall treatment utility compared to standard dosing
Time Frame: 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
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall treatment utility
Time Frame: 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
12 weeks
Progression free survival
Time Frame: 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
up to 60 months
Overall survival
Time Frame: up to 60 months
From date of randomization until the date of death from any cause, assessed up to 60 months
up to 60 months
Quality of life
Time Frame: 12 weeks
measured by QLQ-C30 (general) and QLQ-ELD14 (elderly cancer patients)
12 weeks
Safety
Time Frame: 12 weeks
Adverse events, measured by CTCAE v5.0
12 weeks
Hospital care use
Time Frame: 12 weeks
number of outpatients visits, telephone contacts or hospital admission days
12 weeks
Pharmacokinetic parameters: Cmax
Time Frame: 12 weeks
Peak Plasma Concentration (Cmax)
12 weeks
Pharmacokinetic parameters: AUC
Time Frame: 12 weeks
Area under the plasma concentration versus time curve (AUC)
12 weeks
Pharmacokinetic parameters: Ctrough
Time Frame: 12 weeks
Trough Plasma Concentration (Ctrough)
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Medical Center Groningen

Investigators

  • Principal Investigator: Esther Broekman, MD, University Medical Center Groningen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2024

Primary Completion (Estimated)

March 1, 2025

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

June 19, 2023

First Submitted That Met QC Criteria

July 13, 2023

First Posted (Actual)

July 18, 2023

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16800

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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