NCT07582887 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
| NCT ID | NCT07582887 |
| Status | Recruiting |
| Phase | — |
| Sponsor | Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental |
| Condition | Breast Cancer |
| Study Type | OBSERVATIONAL |
| Enrollment | 70 participants |
| Start Date | 2025-07-15 |
| Primary Completion | 2026-12-31 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
This is an observational study. You will not receive an experimental treatment; researchers will collect data based on your existing condition or standard treatment.
This trial targets 70 participants in total. It began in 2025-07-15 with a primary completion date of 2026-12-31.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
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.
Eligibility Criteria
Inclusion Criteria: * 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. Exclusion Criteria: * Patients who are ultimately not treated with the specified Antibody-Drug Conjugates. * Refusal to provide informed consent for genetic analysis.
Contact & Investigator
Isabel Blancas López-Barajas, MD, PhD
✉ ensayosclinicosom.husc.sspa@juntadeandalucia.es📞 +34 958 023265
Frequently Asked Questions
Who can join the NCT07582887 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, studying Breast Cancer. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
Is NCT07582887 currently recruiting?
Yes, NCT07582887 is actively recruiting participants. Contact the research team at ensayosclinicosom.husc.sspa@juntadeandalucia.es for enrollment information.
Where is the NCT07582887 trial being conducted?
This trial is being conducted at Granada, Spain.
Who is sponsoring the NCT07582887 clinical trial?
NCT07582887 is sponsored by Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental. The trial plans to enroll 70 participants.
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