None listed
Conditions
Brief summary
A multi-site prospective study to implement and evaluate the feasibility of a Pharmacogenetics Screening Program for 5-fluorouracil [5-FU], capecitabine and irinotecan chemotherapies for patients with cancer Who is it for? You may be eligible to join this study if you are aged 18 and above, have been diagnosed with cancer and will receive fluorouracil [5-FU], capecitabine and/or irinotecan chemotherapy for the first time. Study details All participants in this study will receive a genetic screening for DPYD gene test if commencing on 5-FU or capecitabine and/or screening for UGT1A1 gene if commencing on irinotecan anticancer treatment, 7 to 10 days before starting chemotherapy. It is the responsibility and choice of the treating clinician to implement/not implement dosing recommendations based on genetic tests and to manage all aspects of cancer treatment. The feasibility of operating a Pharmacogenetics Screening Program will be assessed using recruitment data from study databases and patient and clinician surveys. Participants will also be followed for up to 12 months to assess toxicities and 24 months to assess treatment response and status. This research will contribute to improve health outcomes for patients with cancer in terms of safety and survival in particular patients who carry altered/deficient genes; dose individualisation prior to administration to 5-FU or capecitabine and/or irinotecan will assist with better tolerance to treatment and hospitalisations (given better toxicity management).
Interventions
The intervention comprises of single time-point pharmacogenetics screening for:
1. DPYD gene test for patients newly commencing on 5-fluorouracil and capecitabine chemotherapy
2. UGT1A1*28 gene test for patients newly commencing on irinotecan chemotherapy
Genetic samples will be collected via blood draw or cheek swab. Interventions will be delivered by a pharmacogenetics pharmacist on referral from the treating medical oncologist. Screening occurs at single time point prior to commencement of
The intervention comprises of single time-point pharmacogenetics screening for: 1. DPYD gene test for patients newly commencing on 5-fluorouracil and capecitabine chemotherapy 2. UGT1A1*28 gene test for patients newly commencing on irinotecan chemotherapy Genetic samples will be collected via blood draw or cheek swab. Interventions will be delivered by a pharmacogenetics pharmacist on referral from the treating medical oncologist. Screening occurs at single time point prior to commencement of 5-fluorouracil, capecitabine or irinotecan. Patients will be followed to cycle 3 of chemotherapy for adverse event, toxicity and health resource utilisation data, and to 12 months after commencement of chemotherapy for response and survival outcomes. All chemotherapy treatments will be administered (dose, route, frequency) according to standard guidelines at the treating institution. Treating clinicians will be provided chemotherapy dosing recommendations based on genetic screening according to protocol specified adjustments based on CPIC/DPWG guidelines, however it is it is the responsibility and choice of the treating clinician to implement/not implement dosing recommendations and to manage all aspects of cancer treatment. Decision to implement/ not implement will be recorded as part of trial outcomes. The study includes 3 main timepoints: 1. TimePoint 1: Baseline visit - Referral details to Pharmacogenetic (PG) screening clinic, consent to PG program testing for DPYD gene +/- UGT1A1 gene testing +/- research sample collection Demographics and clinical characteristics (medical, disease and treatment history) Eastern Cooperative Oncology Group (ECOG) performance status DNA sample (blood or cheek swab) EQ-5D-5L questionnaire for health economic study (QALY) and EORTC QLQ-C30 (version 3) questionnaire will be collected. TimePoint 2: Sample Collection - DNA sample (blood or cheek swab) PG Program sample for DPYD gene +/- UGT1A1 gene testing +/- research sample collection). Note: Patients already completed SOC PG Screening Program (since December 2019) or will be enrolled in the Program will only have research sample taken if have provided consent. Research sample collection for new patients will be collected at a suitable time. TimePoint 3: Follow-up visits which includes follow-up 1 to follow-up 6 as explained below: Follow-up 1 (Pre C1D1 of chemotherapy): Pharmacogenetics Program Pharmacist discusses DPYD gene test results 7 to 10 days after collection of sample with the treating oncologist via email and/or phone call for dose adjustment recommendations and patient. Dose recommendation will be recommended according to the Clinical Pharmacogenetics Implementation Consortium (CPIC) updated guidelines 2018 for DPYD gene test, they have recommended if patients are poor metabolisers to avoid fluoropyrimidines. If patients are DPYD intermediate metabolisers - the CPIC recommendation is for a 50% dose reduction on the intended starting dose of fluoropyrimidine and for dose increases to be made from cycle 3 onwards, depending on tolerability of the first 2 cycles. For UGT1A1*28, dose adjustment will be recommended according to Dutch Pharmacogenetics Working Group (DPWG) 2018 updated guidelines they have precisely stated initial dose reduction of irinotecan by 30% in homozygous (*28/*28) poor metabolizer patients, and the dose can be increased, guided by the neutrophil count. Follow-up 2 (C1D3-C1D7 of chemotherapy): the pharmacogenetics program pharmacist will follow up patients via telehealth or phone call (or in person if they are attending an appointment at primary site) 3 to 7 days post 5-FU or capecitabine Cycle 1 commencement, and coument toxicity data according to according to CTCAE v5.0 and check on adherence to capecitabine tablets. Assist and counsel patients on how to manage side effects and escalate to medical oncologist as required. EQ-5D-5L questionnaire for health economic study (QALY), EORTC QLQ-C30 (version 3) questionnaire and Clinician and patient survey will be collected. Survey/ questionnaires to be completed at suitable time for patients/clinicians. Follow-up 3 and 4 (Pre C2D1 of chemotherapy and Pre-C3D1): medical oncologist will document adverse effects according to CTCAE v5.0 prior to Cycle 2 and prior to Cycle 3 in patient medical record. EQ-5D-5L questionnaire for health economic study (QALY) will be collected preC2 and pre-C3 EORTC QLQ-C30 (version 3) questionnaire will be collected at pre-C3 Follow-up 5 and 6 (at month 6) and (at month 12) : Treatment data, response and status will only be collected from the primary site. The health economic data will be collected upto pre-C3 and patients who cease drug prior to pre C3D1 review will be followed for adverse events and cost data collection until equivalent pre C3D1 review date had they continued on the same treatment regimen. Toxicity data will be collected as per above specified timepoints and cancer and cancer treatment information will be collected during the study.
Sponsors
Peter MacCallum Cancer Centre
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Prevention
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged 18 years or older 2. First time exposure to fluoropyrimidine and/or irinotecan chemotherapy for cancer treatment (any line of treatment, any cancer diagnosis, any stage of disease). 3. Previously enrolled patients in the Peter Mac Pharmacogenetics Screening Program, for purpose of consenting for collection and storage of research samples for future genomic testing.
Exclusion criteria
1. Patients that have had prior exposure to fluoropyrimidine and irinotecan, other than those previously enrolled in the Peter Mac Pharmacogenetics Screening program who are included only for research sample collection. 2. Patients with known DPD deficiency or Gilberts’ syndrome 3. Patients undergoing cytoreduction surgeries and HIPEC planned to receive HIPEC, single dose 5-fluorouracil
Outcome results
None listed