Melanoma Stage IIIADOPTNCT04154163
Appropriate Dosing to Optimise Personalised Cancer Treatments
An observational study of Melanoma Stage III and Melanoma Stage IV, run by University of Dundee at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Melanoma Stage III, Melanoma Stage IV, Ovarian Cancer
- What is being tested?
- Dried blood Spot (DBS) and Venous blood sampling
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Jan 2020to 5 Mar 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Participants will be recruited from the Oncology Unit and Dermatology or Oncology outpatient departments
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
NHS Tayside and University of Dundee
Dundee, Scotland, DD1 9SY
About this study
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.
Read the 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.
- Conditions
- Melanoma Stage III, Melanoma Stage IV, Ovarian Cancer, Renal Cancer Stage III, Renal Cancer Stage IV, Lung Cancer, Non-small Cell
- Being tested
- Dried blood Spot (DBS), Venous blood sampling
- Medical subject headings
- Melanoma, Ovarian Neoplasms, Kidney Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dried blood Spot (DBS)Diagnostic test
Also called DBS home collection kits
Dried Blood Spot filter paper and sponges
Venous blood samplingDiagnostic test
Also called Phlebotomy
Venous blood
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Diagnostic Test: Dried blood Spot (DBS); Diagnostic Test: Venous blood sampling | |
| 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 Receives: Diagnostic Test: Dried blood Spot (DBS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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
Measured: 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 outcomes (5)
The ability of oncology patients receiving targeted cancer treatments to collect multiple DBS samples over a 24-hour period
Successful collection of DBS samples both under supervision in hospital and when at home
Measured: 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
Number of Adverse Events per participant and measures of patient acceptability for collection of DBS
Measured: 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
Demonstration that the drug concentrations measured in fresh and DBS samples stored for several days is the same.
Measured: 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)
Changes in drug levels of co-medications over time following standard clinical dosing with targeted cancer treatments such as dabrafenib +/- trametinib
Measured: 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
Collection of drug tolerability data from examination of clinical pathway for participating patients
Measured: Before recruitment and after commencing relevant medication
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2019
- Study start10 Jan 2020
- Primary completion5 Mar 2021
- Study completion5 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Melanoma Stage IIIStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charlotte Proby, MBBS,FRCP, Principal investigator, Chief Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04154163
- Sponsor's protocol ID
- 2-032-19
- Acronym
- ADOPT
- Status last verified
- Feb 2022
- First submitted
- 31 Oct 2019
- Last updated
- 28 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: De-identified individual participants data for full primary and secondary outcome measures maybe be made available
Publications
Robijns K, Koster RA, Touw DJ. Therapeutic drug monitoring by dried blood spot: progress to date and future directions. Clin Pharmacokinet. 2014 Nov;53(11):1053. doi: 10.1007/s40262-014-0197-3. No abstract available.
PubMed 25312497de Wit D, den Hartigh J, Gelderblom H, Qian Y, den Hollander M, Verheul H, Guchelaar HJ, van Erp NP. Dried blood spot analysis for therapeutic drug monitoring of pazopanib. J Clin Pharmacol. 2015 Dec;55(12):1344-50. doi: 10.1002/jcph.558. Epub 2015 Jul 14.
PubMed 26032288Nijenhuis CM, Huitema AD, Marchetti S, Blank C, Haanen JB, van Thienen JV, Rosing H, Schellens JH, Beijnen JH. The Use of Dried Blood Spots for Pharmacokinetic Monitoring of Vemurafenib Treatment in Melanoma Patients. J Clin Pharmacol. 2016 Oct;56(10):1307-12. doi: 10.1002/jcph.728. Epub 2016 Apr 8.
PubMed 26918324Ouellet D, Gibiansky E, Leonowens C, O'Hagan A, Haney P, Switzky J, Goodman VL. Population pharmacokinetics of dabrafenib, a BRAF inhibitor: effect of dose, time, covariates, and relationship with its metabolites. J Clin Pharmacol. 2014 Jun;54(6):696-706. doi: 10.1002/jcph.263. Epub 2014 Jan 17.
PubMed 24408395Friedl B, Kurlbaum M, Kroiss M, Fassnacht M, Scherf-Clavel O. A method for the minimally invasive drug monitoring of mitotane by means of volumetric absorptive microsampling for a home-based therapeutic drug monitoring. Anal Bioanal Chem. 2019 Jul;411(17):3951-3962. doi: 10.1007/s00216-019-01868-1. Epub 2019 May 16.
PubMed 31093700
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Appropriate Dosing to Optimise Personalised Cancer Treatments
- ClinicalTrials.gov ID
- NCT04154163
- Acronym / sponsor ID
- ADOPT / 2-032-19
- Conditions
- Melanoma Stage III, Melanoma Stage IV, Ovarian Cancer, Renal Cancer Stage III, Renal Cancer Stage IV, Lung Cancer, Non-small Cell
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Study start
- 10 Jan 2020 (actual)
- Primary completion
- 5 Mar 2021 (actual)
- Study completion
- 5 Mar 2021 (actual)
- First posted
- 6 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stage 1 Participants | – | Diagnostic Test: Dried blood Spot (DBS), Diagnostic Test: Venous blood samplingBlood 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 |
| Stage 2 Participants | – | Diagnostic Test: Dried blood Spot (DBS)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 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Participants will be recruited from the Oncology Unit and Dermatology or Oncology outpatient departments
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dried blood Spot (DBS)Also: DBS home collection kitsDried Blood Spot filter paper and sponges | Diagnostic test | Stage 1 Participants, Stage 2 Participants |
| Venous blood samplingAlso: PhlebotomyVenous blood | Diagnostic test | Stage 1 Participants |
Primary outcome
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
5 secondary outcomes
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
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
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.
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
Drug tolerability collected from examination of clinical pathway for participating patients
Time frame: Before recruitment and after commencing relevant medication
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2022.
- Background: PubMed 25312497Robijns K, Koster RA, Touw DJ. Therapeutic drug monitoring by dried blood spot: progress to date and future directions. Clin Pharmacokinet. 2014 Nov;53(11):1053. doi: 10.1007/s40262-014-0197-3. No abstract available.
- Background: PubMed 26032288de Wit D, den Hartigh J, Gelderblom H, Qian Y, den Hollander M, Verheul H, Guchelaar HJ, van Erp NP. Dried blood spot analysis for therapeutic drug monitoring of pazopanib. J Clin Pharmacol. 2015 Dec;55(12):1344-50. doi: 10.1002/jcph.558. Epub 2015 Jul 14.
- Background: PubMed 26918324Nijenhuis CM, Huitema AD, Marchetti S, Blank C, Haanen JB, van Thienen JV, Rosing H, Schellens JH, Beijnen JH. The Use of Dried Blood Spots for Pharmacokinetic Monitoring of Vemurafenib Treatment in Melanoma Patients. J Clin Pharmacol. 2016 Oct;56(10):1307-12. doi: 10.1002/jcph.728. Epub 2016 Apr 8.
- Background: PubMed 24408395Ouellet D, Gibiansky E, Leonowens C, O'Hagan A, Haney P, Switzky J, Goodman VL. Population pharmacokinetics of dabrafenib, a BRAF inhibitor: effect of dose, time, covariates, and relationship with its metabolites. J Clin Pharmacol. 2014 Jun;54(6):696-706. doi: 10.1002/jcph.263. Epub 2014 Jan 17.
- Background: PubMed 31093700Friedl B, Kurlbaum M, Kroiss M, Fassnacht M, Scherf-Clavel O. A method for the minimally invasive drug monitoring of mitotane by means of volumetric absorptive microsampling for a home-based therapeutic drug monitoring. Anal Bioanal Chem. 2019 Jul;411(17):3951-3962. doi: 10.1007/s00216-019-01868-1. Epub 2019 May 16.
- Individual participant dataSharing planned: No. De-identified individual participants data for full primary and secondary outcome measures maybe be made available
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charlotte Proby, MBBS,FRCP principal investigator
Chief Investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Melanoma Stage III and Melanoma Stage IV, run by University of Dundee at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04154163, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2022.