Appropriate Dosing to Optimise Personalised Cancer Treatments
Condition: Melanoma Stage III; Melanoma Stage IV; Ovarian Cancer; Renal Cancer Stage III; Renal Cancer Stage IV; Lung Cancer, Non-small Cell
MeSH terms: Melanoma; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung
Study type: Observational

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.
    

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.
    

Intervention name(s): Dried blood Spot (DBS); Venous blood sampling
Intervention type(s): Diagnostic Test; Diagnostic Test
Intervention description(s): Dried Blood Spot filter paper and sponges; Venous blood
Other intervention name(s): DBS home collection kits; Phlebotomy
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Participants will be recruited from the Oncology Unit and Dermatology or Oncology
        outpatient departments
      
Biospecimen description: 
      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.