Appropriate Dosing to Optimise Personalised Cancer Treatments

NCT04154163 | Completed

• 1 other identifier: 2-032-19
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma Stage III; Melanoma Stage IV; Ovarian Cancer; Renal Cancer Stage III; Renal Cancer Stage IV; Lung Cancer, Non-small Cell

Outcome Measures

Primary Outcomes (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

  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 Outcomes (5)

• The ability of oncology patients receiving targeted cancer treatments to collect multiple DBS samples over a 24-hour period

  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

  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

  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)

  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

  Before recruitment and after commencing relevant medication

Study Arms (2)

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); 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

Diagnostic Test: Dried blood Spot (DBS)

Interventions

Dried blood Spot (DBS) DIAGNOSTIC_TEST

Dried Blood Spot filter paper and sponges

Also known as: DBS home collection kits

Stage 1 Participants; Stage 2 Participants

Venous blood sampling DIAGNOSTIC_TEST

Venous blood

Also known as: Phlebotomy

Stage 1 Participants

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Dundee: lead

Study Sites (1)

NHS Tayside and University of Dundee

Dundee, Scotland, DD1 9SY, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 25312497 BACKGROUND

• de 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.

  PMID: 26032288 BACKGROUND

• Nijenhuis 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.

  PMID: 26918324 BACKGROUND

• Ouellet 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.

  PMID: 24408395 BACKGROUND

• Friedl 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.

  PMID: 31093700 BACKGROUND

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.

MeSH Terms

Conditions

Melanoma; Ovarian Neoplasms; Kidney Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Dried Blood Spot Testing; Blood Specimen Collection; Phlebotomy

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical Analysis; Clinical Chemistry Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Specimen Handling; Punctures; Surgical Procedures, Operative; Therapeutics

Study Officials

• Charlotte Proby, MBBS,FRCP

  Chief Investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2019
• First Posted: November 6, 2019
• Study Start: January 10, 2020
• Primary Completion: March 5, 2021
• Study Completion: March 5, 2021
• Last Updated: February 28, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)