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Appropriate Dosing to Optimise Personalised Cancer Treatments (ADOPT)

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ClinicalTrials.gov Identifier: NCT04154163
Recruitment Status : Recruiting
First Posted : November 6, 2019
Last Update Posted : January 13, 2020
Sponsor:
Information provided by (Responsible Party):
Charlotte Proby, University of Dundee

Brief 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.

Condition or disease Intervention/treatment
Melanoma Stage III Melanoma Stage IV Ovarian Cancer Renal Cancer Stage III Renal Cancer Stage IV Lung Cancer, Non-small Cell Diagnostic Test: Dried blood Spot (DBS) Diagnostic Test: Venous blood sampling

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.

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Study Type : Observational
Estimated Enrollment : 25 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Appropriate Dosing to Optimise Personalised Cancer Treatments
Actual Study Start Date : January 10, 2020
Estimated Primary Completion Date : July 30, 2020
Estimated Study Completion Date : December 31, 2020


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 Name: DBS home collection kits

Diagnostic Test: Venous blood sampling
Venous blood
Other Name: 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 Name: DBS home collection kits




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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


Biospecimen Retention:   Samples Without DNA

Biospecimens will be blood tests conducted in the form of either (i) whole blood which will be collected using Dried Blood Spots "DBS" +/- and (ii) venous blood samples.

Stage 1:

Five patients will be recruited for initial validation of drug dose measurements using the DBS method by comparison with venous blood samples.

One or two drops of blood (10 microlitres) collected using triplicates of blood spots on to dry blood spot filter paper and micro-sampler sponge at specified time intervals.

A phlebotomy serum sample (5 ml) will be collected in a heparin tube at the same time intervals before and after oral dosing of their targeted drugs over a single 24-hour period.

Stage 2:

One or two drops of blood (10 microlitres) collected using triplicates of blood spots on to dry blood spot filter paper and micro-sampler sponge at specified time intervals.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participants will be recruited from the Oncology Unit and Dermatology or Oncology outpatient departments
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04154163


Contacts
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Contact: Angela Alani, MB Bch BAO 07490192716 a.alani@dundee.ac.uk
Contact: Charlotte Proby, MBBS,FRCP 01382383289 ext 83289 c.proby@dundee.ac.uk

Locations
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United Kingdom
NHS Tayside and University of Dundee Recruiting
Dundee, Scotland, United Kingdom, DD1 9SY
Contact: Charlotte Proby, BA MBBS FRCP    01382383289 ext 83289    c.proby@dundee.ac.uk   
Contact: Angela Alani, MB Bch BAO, MRCP Derm    07490192716 ext 36453    a.alani@dundee.ac.uk   
Sponsors and Collaborators
University of Dundee
Investigators
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Principal Investigator: Charlotte Proby, MBBS,FRCP Chief Investigator

Publications:
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Responsible Party: Charlotte Proby, Professor, University of Dundee
ClinicalTrials.gov Identifier: NCT04154163    
Other Study ID Numbers: 2-032-19
First Posted: November 6, 2019    Key Record Dates
Last Update Posted: January 13, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: De-identified individual participants data for full primary and secondary outcome measures maybe be made available

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Neoplasms by Site
Urogenital Neoplasms
Urologic Neoplasms
Neoplasms, Glandular and Epithelial
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Melanoma
Carcinoma, Renal Cell
Carcinoma, Non-Small-Cell Lung
Nevi and Melanomas
Kidney Diseases
Urologic Diseases
Adenocarcinoma
Carcinoma
Carcinoma, Bronchogenic
Lung Diseases
Respiratory Tract Diseases