Prospective Phase 0 Pilot Study, Assessing Potential Interest of [68Ga]Ga-PentixaFor PET/CT in Metastatic Triple Negative Breast Cancer Patients
Triple-negative breast cancer (TNBC) is a particularly aggressive type of breast cancer that is difficult to treat. Unlike other forms of breast cancer, TNBC tends to relapse earlier and spread more quickly to other parts of the body. Unfortunately, patients with TNBC have a lower survival rate, often less than five years after diagnosis. This highlights the urgent need for better treatments for TNBC. One of the main challenges in treating TNBC is that it lacks certain receptors that other breast cancers have. These receptors are usually targeted by specific therapies, making TNBC harder to treat with targeted approaches. Currently, a type of imaging called \[18F\]FDG PET/CT is the most accurate method for detecting breast cancer and its spread. However, with the rise of personalized medicine, there is a growing interest in molecular targeted approaches. These methods aim to provide highly specific diagnostics and treatments based on the unique characteristics of each patient's cancer. One promising target for these new approaches is a receptor called CXCR4. CXCR4 is found on the surface of many cells and is involved in various processes in the body. It is often overexpressed in different types of cancer, including breast cancer. Research has shown that CXCR4 levels are higher in metastatic sites (where cancer has spread) compared to primary tumors. CXCR4 is not only present in cancer cells but also in immune cells within the tumor environment. In invasive breast cancer, CXCR4 plays a crucial role in tumor migration, invasiveness, metastasis, and proliferation. A clinical study evaluated 18 breast cancer patients using a new imaging method called \[68Ga\]Ga-PentixaFor PET/CT or PET/MR. They found that this method showed higher uptake in breast cancer cases with poorer prognosis compared to the traditional \[18F\]FDG PET/CT. Higher CXCR4 expression is particularly seen in TNBC compared to other breast cancer subtypes. The goal of the study is to assess how \[68Ga\]Ga-PentixaFor is distributed in the body using PET/CT imaging. This will help demonstrate the potential of CXCR4 as a promising target for new treatments. If successful, \[68Ga\]Ga-PentixaFor PET/CT could become a valuable tool for identifying patients who might benefit from treatments using \[177Lu\]/\[90Y\] PentixaTher.
• Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.
• Female or male, Age ≥ 18 years at time of study entry.
• Primitive triple negative breast cancer proven histologically, defined according to the following criteria:
‣ Estrogen receptors \<10%.
⁃ And progesterone receptors \<10%.
⁃ And HER2 not amplified or not overexpressed.
• Recurrence metastatic Breast Cancer or De Novo metastatic Breast Cancer documented by \[18F\]FDG PET/CT ± conventional imaging with at least one measurable metastasis according to PERCIST and/or RECIST.
• ECOG performance status \< 2.
• Negative serum/urine pregnancy test prior to \[68Ga\]Ga-PentixaFor administration for female patient of childbearing potential\*.
• Consent to use a contraception method for at least 3 months after each administration of \[68Ga\]Ga-PentixaFor (as defined in Appendix 7 and according to local guidelines).
• Adequate Organ function confirmed by laboratory tests results allowing for safe administration of \[68Ga\]Ga- PentixaFor:
• Hematologic function: Absolute Neutrophil Count (ANC) of ≥ 1.5 x 109 /L, platelet count of ≥ 100 x 109 /L, and hemoglobin of ≥ 9 g/dL).
• Hepatic function: AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases).
• Renal function: Estimated Glomerular Filtration Rate (eGFR) ≥ 50 mL/min/1.73m², as calculated using the CKD-EPI or MDRD equation.Life expectancy at least 3 months.
⁃ Patient has valid health insurance.
⁃ Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
∙ Note: a female participant of childbearing potential is a woman who is not permanently sterilized or not postmenopausal (postmenopausal is defined as 12 months with no menses without an alternative medical cause).