NCT07582887Recruiting
Impact of Genetic Variants on the Toxicity of Antibody-Drug Conjugates in Locally Advanced or Metastatic Breast Cancer: The Role of the UGT1A1 Gene as a Predictive Biomarker of Therapeutic Response
Source: ClinicalTrials.gov · Last updated 13 May 2026
Brief summary (registry, in English)
The metabolism of anticancer drugs is influenced by genetic variants that affect their bioavailability and toxicity. In the case of antibody-drug conjugates (ADCs), such as sacituzumab-govitecan (SG), trastuzumab-deruxtecan (T-DXd), and datopotamab-deruxtecan (Dato-DXd), the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) plays a central role in the glucuronidation and elimination of their cytotoxic components. In particular, the metabolism of SN-38, the active metabolite of irinotecan and SG, is highly influenced by variants in UGT1A1, leading to drug accumulation and the development of severe toxicities. Patients with variants such as UGT1A1\*28 (rs3064744) and UGT1A1\*6 (rs4148323) exhibit reduced enzyme activity, increasing the risk of neutropenia and severe diarrhea. The relevance of UGT1A1 is not limited to sacituzumab-govitecan; its role in the elimination of camptothecin derivatives suggests it could also impact the toxicity of trastuzumab-deruxtecan and datopotamab-deruxtecan, which contain deruxtecan, a cytotoxic agent 10 times more potent than irinotecan. Despite strong evidence linking the UGT1A1 genotype to irinotecan toxicity, there are currently no established pharmacogenetic recommendations for antidiuretic peptides (ADCs) in metastatic breast cancer.
- Status (registry)
- Recruiting
- Study type
- Observational
- Enrollment
- 70 (estimated)
- First submitted
- 6 May 2026
- Start date
- 15 Jul 2025
- Primary completion date
- 31 Dec 2026
- Lead sponsor
- Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental
- Diseases
- Metastatic breast cancer
- NCT number
- NCT07582887
What you commit to
- Study type: Observational
- Planned participants: 70
- From 15 Jul 2025 to the primary completion date, 31 Dec 2026
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Patients who are ultimately not treated with the specified Antibody-Drug Conjugates.
Other
- Refusal to provide informed consent for genetic analysis.
Who the study is looking for
- Patients aged 18 years or older.
- Patients diagnosed with breast cancer starting or undergoing treatment with Sacituzumab Govitecan, Trastuzumab Deruxtecan, or Datopotamab Deruxtecan.
- Provision of signed informed consent for the genetic study.
Age in the registry: 18 years to - · Sex: All · Does not accept healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Hospital Universitario Clínico San Cecilio Coordinator of this site? Confirm its status | Granada | Spain | Recruiting |
This page is information, not medical advice. Discuss any trial with your doctor.