Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Melanoma

Carcinoma, Renal Cell

Kidney Neoplasms

Carcinoma

Carcinoma, Non-Small-Cell Lung

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urogenital Neoplasms

Urologic Neoplasms

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Renal Cell Carcinoma

Neuroendocrine Tumor

Neuroepithelioma

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

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

Dried Blood Spot filter paper and sponges

Dried blood Spot (DBS)

Venous blood sampling

Charlotte Proby, MBBS,FRCP

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.

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.

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.

Appropriate Dosing to Optimise Personalised Cancer Treatments

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

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

Successful collection of DBS samples both under supervision in hospital and when at home

Number of Adverse Events per participant and measures of patient acceptability for collection of DBS

Demonstration that the drug concentrations measured in fresh and DBS samples stored for several days is the same.

Changes in drug levels of co-medications over time following standard clinical dosing with targeted cancer treatments such as dabrafenib +/- trametinib

Collection of drug tolerability data from examination of clinical pathway for participating patients

University of Dundee

Spots Global Cancer Trial Database for dried blood spot (dbs)