Appropriate Dosing to Optimise Personalised Cancer Treatments (ADOPT)

February 25, 2022 updated by: University of Dundee
This is a pilot study to assess feasibility of dried blood spot (DBS) samples for pharmacokinetic measurements of targeted anti-cancer drugs in oncology patients such as patients with BRAF-mutant melanoma receiving targeted treatment with BRAF and MEK inhibitors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In the pharmacology laboratory, we have developed a method for measuring drug concentrations in animals using dried blood spots (DBS). DBS is a simple method that could be easily carried out by patients at home, using either filter paper-based DBS cards (e.g. Whatman 903, FTA DMPK-C) or small sponges (www.neoteryx.com).

The routine use of DBS to clinically test blood was first used in the 1960s as a safe and simple method of testing for inherited metabolic disorders in new born babies. However, in recent years there has been increasing use of DBS to test blood for other things, including for drugs as a way to monitor the drug level in the blood.

This method has great potential application in testing blood for drug levels in cancer patients. We wish to establish if this DBS technique is feasible in real-life practice for cancer patients on targeted anti-cancer therapies as should this be the case this innovation could herald a new era in personalised treatment of advanced human cancers allowing doctors to more safely use combinations of targeted therapies. These combinations of targeted therapies have been shown to inhibit development of drug resistance and are increasingly being used in clinical practice. However, targeted therapies often fail (especially combinations of targeted therapies) because of unacceptable toxicities making them intolerable for the patient. With an easy and acceptable method for monitoring the drug level in blood, as could be provided by DBS, the right amount of drug could be given to each individual patient and this 'personalised' drug dosing as standard of care might result in much greater success with combinations of anti-cancer drugs.

This drug monitoring is especially important for targeted anti-cancer therapies because many of these (such as Dabrafenib, used for many cases of advanced melanoma) have profound affects on the liver enzymes that metabolise (get rid of) most medications. Dabrafenib is a potent inducer of P450 liver enzymes and this induction means that other drugs metabolised by the same liver pathway (the great majority of drugs are metabolised by the same pathways) will have significantly reduced blood levels if the patient is on Dabrafenib. So it is especially important to be able to monitor blood levels of both Dabrafenib and of other co-medications that the patient may be taking. The DBS sampling method would allow this and would provide a safe, convenient and cheap test that could be conducted in the patient's home and posted back to the laboratory.

Study Type

Observational

Enrollment (Actual)

18

Contacts and Locations

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

Study Locations

  • United Kingdom
    • Scotland
      • Dundee, Scotland, United Kingdom, DD1 9SY
        • NHS Tayside and University of Dundee

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

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Participants will be recruited from the Oncology Unit and Dermatology or Oncology outpatient departments

Description

Inclusion Criteria:

  • Male or female participants
  • Age 18 years and over
  • Confirmed diagnosis of stage 4 or stage 3 unresectable cancers; BRAF+ melanoma, c-KIT+ melanoma, advanced renal cell carcinoma, non-small cell lung carcinoma and ovarian carcinoma.
  • Able to perform study assessments
  • Individuals who are participating in the follow-up phase of another interventional trial/study, or who are enrolled in an observational study, will be co-enrolled where the CIs of each study agree that it is appropriate

Exclusion Criteria:

  • Inability to give informed consent
  • World Health Organisation (WHO) performance status 3-4
  • Known allergy or intolerance to Dabrafenib +/- Trametinib, Prazopanib, Erlotinib, Gefitinib, Imatinib, Osimertinib or Olaparib
  • Unstable co-morbidities; cardiovascular disease e.g. severe congestive cardiac failure, end stage renal failure, hepatic impairment, vasculopathy, inflammatory arthritis or interstitial lung disease/ pneumonitis which, in the opinion of the CI, would make the patient unsuitable to be enrolled in the study
  • Language barrier preventing adequate understanding of the study and a lack of suitable translator service to overcome this barrier
  • Pregnancy

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Stage 1 Participants

Blood test Day 1 DBS and venous blood

Blood test Day 2 DBS (+/- and venous blood)

Blood test Day 15 DBS only

Blood test Day 16 DBS only
Diagnostic test: Dried blood Spot (DBS)
Dried Blood Spot filter paper and sponges
Other Names:
  • DBS home collection kits
Diagnostic test: Venous blood sampling
Venous blood
Other Names:
  • Phlebotomy
Stage 2 Participants

Non-drug naive participants:

Blood test Day 1 DBS

Blood test Day 2 DBS

Blood test Day 15 DBS

Blood test Day 16 DBS

Drug naive participants:

Blood test Day 1 DBS

Blood test Day 2 DBS

Blood test Day 3, 4, or 5 DBS

Blood test Day 4, 5 or 6 DBS

Blood test Day 15 DBS

Blood test Day 16 DBS
Diagnostic test: Dried blood Spot (DBS)
Dried Blood Spot filter paper and sponges
Other Names:
  • DBS home collection kits

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The accuracy of DBS for measuring drug levels in venous blood following standard doses of targeted therapies for metastatic cancers such as BRAF mutant melanoma
Time Frame: Pre-dose,1 hour, 2 hours, 8 hours (if on a once daily drug regime) or pre-second dose (if on a twice daily drug regime) and 24 hours post-dosing
Concentration of targeted anti-cancer drug in venous blood at timed intervals following oral dosing in standard clinical care pathway measured in venous blood and by DBS
Pre-dose,1 hour, 2 hours, 8 hours (if on a once daily drug regime) or pre-second dose (if on a twice daily drug regime) and 24 hours post-dosing

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The ability of oncology patients receiving targeted cancer treatments to collect multiple DBS samples over a 24-hour period
Time Frame: Pre-dose,1 hour, 2 hours, 8 hours (if on a once daily drug regime) or pre-second dose (if on a twice daily drug regime) and 24 hours post-dosing
Successful collection of DBS samples both under supervision in hospital and when at home
Pre-dose,1 hour, 2 hours, 8 hours (if on a once daily drug regime) or pre-second dose (if on a twice daily drug regime) and 24 hours post-dosing
The safety and acceptability of DBS collections at timed intervals before and after taking anti-cancer targeted drugs
Time Frame: After each 24-hour period of DBS sampling and during telephone consultations in weeks 1 and 4
Number of Adverse Events per participant and measures of patient acceptability for collection of DBS
After each 24-hour period of DBS sampling and during telephone consultations in weeks 1 and 4
The stability of the drug levels stored in DBS, taken by the patient at home and posted to the laboratory
Time Frame: Measurement of repeat samples at the timepoints chosen at 1, 2 and 3-days post-collection to ensure stability.
Demonstration that the drug concentrations measured in fresh and DBS samples stored for several days is the same.
Measurement of repeat samples at the timepoints chosen at 1, 2 and 3-days post-collection to ensure stability.
Examine inter-patient variability in Pharmacokinetics (PK)
Time Frame: Measurement of co-medication drug levels at repeat time intervals (Pre-dose,1-hour, 2-hours, 8-hours (once-daily drug regime) or pre-second dose (twice-daily drug regime) and 24-hours post-dosing both before and after starting targeted Dabrafenib
Changes in drug levels of co-medications over time following standard clinical dosing with targeted cancer treatments such as dabrafenib +/- trametinib
Measurement of co-medication drug levels at repeat time intervals (Pre-dose,1-hour, 2-hours, 8-hours (once-daily drug regime) or pre-second dose (twice-daily drug regime) and 24-hours post-dosing both before and after starting targeted Dabrafenib
Drug tolerability collected from examination of clinical pathway for participating patients
Time Frame: Before recruitment and after commencing relevant medication
Collection of drug tolerability data from examination of clinical pathway for participating patients
Before recruitment and after commencing relevant medication

Collaborators and Investigators

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

Sponsor

University of Dundee

Investigators

  • Principal Investigator: Charlotte Proby, MBBS,FRCP, Chief Investigator

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

January 10, 2020

Primary Completion (Actual)

March 5, 2021

Study Completion (Actual)

March 5, 2021

Study Registration Dates

First Submitted

October 31, 2019

First Submitted That Met QC Criteria

November 4, 2019

First Posted (Actual)

November 6, 2019

Study Record Updates

Last Update Posted (Actual)

February 28, 2022

Last Update Submitted That Met QC Criteria

February 25, 2022

Last Verified

February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2-032-19

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

De-identified individual participants data for full primary and secondary outcome measures maybe be made available

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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