UGT1A1*1*1

P1/2, N=34, Completed, University of Michigan Rogel Cancer Center | Active, not recruiting --> Completed | Trial completion date: May 2025 --> Nov 2024 | Trial primary completion date: May 2025 --> Nov 2024

P1/2, N=60, Active, not recruiting, MedPacto, Inc. | Phase classification: P1b/2a --> P1/2 | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Oct 2022 --> May 2024

To date, the clinical benefit and utility of implementing a DPYD/UGT1A1 pharmacogenetic-informed therapy with fluoropyrimidines and/or irinotecan have not been prospectively investigated...Clinical benefit did not appear to be affected. ClinicalTrials.gov Identifier: NCT03093818.

PGx screening and prescribing were feasible in routine oncology care and improved patient outcomes. Findings may inform expanded PGx programs within cancer and other disease settings.

P2, N=50, Active, not recruiting, Fudan University | Recruiting --> Active, not recruiting | Trial primary completion date: Jul 2024 --> Jul 2025

This study will determine the prevalence of DPYD gene variant status in Australia and its impact on FP-induced toxicity among Australians with cancer. Feasibility and cost-effectiveness for Australian health care system will be estimated to support national roll-out of prospective DPYD genotyping prior to FP administration. Additionally, feasibility will be confirmed with the intention of including UGT1A1 in future pharmacogenomic panels to aid chemotherapy prescribing.

Our systematic review and meta-analysis confirmed that SG confers good clinical activity in certain solid tumor types and was tolerable with minimal adverse events. The potential utility of UGT1A1*28 genotyping in predicting clinical response and outcomes could not be determined due to the limited number of studies with available UGT1A1 genotype data.

P2, N=80, Recruiting, OncoSil Medical Limited | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1, N=30, Recruiting, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

SXD had a prophylactic effect in the diarrhea induced by irinotecan, especially for UGT1A1 high-risk population, and this effect from SXD appeared to be maintained the completion of chemotherapy schedule. The mechanism of action of SXD was related to the regulation of inflammatory factors. Trial registration Chinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. https://www.chictr.org.cn/showproj.html?proj=25250 . The preliminary protocol of this clinical study has been published in the journal "Trials" in the form of protocol before this paper (Deng et al. in Trials 21:370, 2020).

This study identified the active components of Astragalus membranaceus and their corresponding targets in CRC. These findings provide robust evidence for precision drug therapy in patients with CRC.

Reporting PGx variants from germline WGS relevant to patients with cancer alongside primary findings related to their cancer can be clinically informative, informing prescribing to reduce the risk of ADRs. Extending the range of actionable variants to those found in patients of non-European ancestry is important and will extend the potential clinical impact.

P1/2, N=64, Recruiting, National Cancer Institute (NCI) | Not yet recruiting --> Recruiting

We previously developed Caco-2 cells whose expression of CYP3A4 can be controlled using doxycycline (Dox) (CYP3A4-Caco-2 cells) (Ichikawa et al., Sci...In this study, we used genome-editing technology to establish CES1-knockout Caco-2 cells whose CYP3A4 and UGT1A1 expression can be regulated by the Tet-Off system. These cell lines would be useful in pharmaceutical researches, including intestinal toxicological studies, as an in vitro model for orally administered drugs.

PU mitigates DB-induced liver injury by regulating the expression of drug transporters and modulating the Nrf2/NF-κB/Bcl-2 signaling pathway.

Standard first-line chemotherapy in small cell lung cancer (SCLC) is based on the platinum plus etoposide combination...Our results provide evidence that ERCC1 and ERCC2 variants may predict the efficacy and safety of platinum-based chemotherapy in SCLC patients. LS-SCLC patients may benefit most from ERCC1 determination, but prospective studies are needed.

SG RP2D was established as 10 mg/kg in Japanese patients. SG showed efficacy in Japanese patients with previously treated mTNBC, a manageable safety profile, and no new safety signals, consistent with the previous ASCENT study.

P3, N=968, Active, not recruiting, Stichting Hemato-Oncologie voor Volwassenen Nederland | Recruiting --> Active, not recruiting | Trial completion date: May 2034 --> Sep 2034 | Trial primary completion date: Oct 2024 --> Apr 2027

P=N/A, N=16, Active, not recruiting, University of Michigan Rogel Cancer Center | Recruiting --> Active, not recruiting | N=96 --> 16

Methods Pts with cT2-4N0M0 MIBC with pure/predominant urothelial carcinoma histology, who were ineligible for or refused cisplatin-based chemotherapy, received 4 cycles of SG 10 mg/kg (days 1,8 q3w) followed by RC. Conclusions The observed ypT0N0-x responses after neoadjuvant SG demonstrate promising activity in MIBC, unveiling a potential to avoid RC. Reduced dose of SG was feasible, and the data support the ongoing SURE-01 study in MIBC.

In particular, it also potently inhibited SN-38, the active metabolite of irinotecan, glucuronidation in HLMs with an IC50 value of 3.84 ± 0.46 μM. The prediction results showed that darolutamide may increase the risk of DDIs when administered in combination with substrates of UGT1A1, UGT1A7, or UGT2B15. Therefore, the combined administration of darolutamide and drugs metabolized by the above UGTs should be used with caution to avoid the occurrence of potential DDIs.

P1, N=60, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Aug 2025

Implementation of a pharmacist-guided pharmacogenomics based dosing service aided in optimizing drug therapy and has positioned Dartmouth Health for further expansion of pharmacogenomics and personalized patient care.

P2, N=182, Terminated, NuCana plc | Trial completion date: Mar 2025 --> Aug 2024 | Active, not recruiting --> Terminated; A pre-planned initial analysis concluded that the study was unlikely to achieve its primary objective of demonstrating superior progression-free survival. Based on the Steering Committee's recommendation, the Sponsor has closed the study.

P1/2, N=60, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2027 --> Sep 2025

P2, N=60, Not yet recruiting, National Cancer Institute (NCI)

Patients with UGT1A1*6 or *28 (+/+) should be especially concerned about neutropenia and leukopenia during nal-IRI/FL treatment. Additionally, high AST value and pancreatic head cancer may be risk factors for leukopenia during nal-IRI/FL treatment.

Hence, screening for UGT1A1 polymorphisms before irinotecan-based chemotherapy is recommended to minimize toxicity, whereas liposomes offer the potential to deliver irinotecan with fewer side effects in patients with pancreatic ductal adenocarcinoma. This review presents a comprehensive overview of the effects of genotype-guided dosing of irinotecan on UGT1A1*28 and UGT1A1*6 variants, incorporating pharmacogenomic research, optimal regimens for metastatic colorectal and pancreatic cancer treatment using irinotecan, guidelines for toxicity reduction, and an evaluation of the cost-effectiveness of UGT1A1 genotype testing.

Application of PGx significantly reduced rates of SAEs in patients with cancer. Emergent medicine-variant pairs herald further research into the expansion and optimization of PGx to improve systemic anti-cancer and supportive care medicine safety and efficacy.

P3; Active, not recruiting --> Completed

Based on the mechanisms, we further outline the potential biomarkers for predicting the severity of diarrhea. Finally, based on the current experimental evidence in preclinical and clinical studies, we discuss and prospect the current and emerging strategies for the prevention of irinotecan-induced diarrhea.

This study provides the first comprehensive pharmacogenetic characterization of cancer therapy-related SNPs and highlights significant disparities in SNP frequencies within the Chilean population. Our findings underscore the necessity for inclusive research and personalized therapeutic strategies to ensure the equitable and effective application of precision medicine across diverse global communities.

These analyses support the approved SG dosing regimen of 10 mg/kg as intravenous infusion on days 1 and 8 of 21-day cycles and did not identify a need for dose adjustment based on evaluated covariates or disease characteristics.

The UGT1A1 level may be a biomarker for early diagnosis of cancer. Meanwhile, UGT1A1 plays a crucial role in pancreatic cancer, and the combination of chrysin and cisplatin may provide effective ideas for pancreatic cancer treatment.

P2, N=182, Active, not recruiting, NuCana plc | Recruiting --> Active, not recruiting

Real-world TIC incidence is higher compared to randomized clinical trials and biomarkers with potential predictive value aren't available. Our preliminary data, as proof of concept, could suggest a predictive role of pharmacogenomic approach in the identification of cardiotoxicity risk biomarkers for anti-HER2 treatment.

One hundred and seven patients received irinotecan treatment and three patients with AA type received paclitaxel treatment. Individual irinotecan treatment shows encouraging survival and tolerability outcomes in patients with GG/GA subtype. Irinotecan may be not suitable for patients with AA subtype.

Silencing of Pxr further confirmed that OA-mediated upregulation of proliferation-related proteins depended on PXR. The current study illustrated that OA exhibited a significant promoting effect on liver regeneration following PHx, potentially through regulation of the PXR signaling pathway to accelerate liver recovery.

This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.

The precise description of the allelic distribution of the variants of interest in our reference populations is information of great interest for the management of the prescription of these antineoplastic drugs. We characterized the allelic distribution of the UGT1A1*28 variant (rs3064744), as well as the DPYD*2A (rs3918290) variant, c.1679T>G (rs55886062), c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in series of 5251 patients who are going to receive treatment with irinotecan and fluoropyrimidines, representative of Valencian, Aragonese and Western Andalusian populations.

These hepatic impairment effects reduced between-subject variability by only 5%-8% for their respective parameter, with a large amount of remaining unexplained variability. With further validation, this model can be leveraged to assess the need for dose adjustments in this patient population.

P1, N=40, Completed, Celgene | Active, not recruiting --> Completed