Heterogeneity of 68Ga-FAPI Uptake As Imaging Biomarker in T-DXd Treatment for Brain Metastasis of HER2 Positive Breast Cancer

Phase 2

Not yet recruiting

• Conditions: Metastatic Breast Cancer; Breast Cancer
• Interventions: Drug: Trastuzumab deruxtecan (T-DXd)

• Registration Number: NCT06797622
• Lead Sponsor: Fudan University

Brief Summary

The purpose of this study was to explore the predictive value of the heterogeneity of 68Ga-FAPI PET-CT uptake before treatment on the response of T-DXd treatment in patients with brain metastases of HER2-positive breast cancer. The patient underwent 68Ga-FAPI PET-CT examinations within 2 weeks before and after 2 cycles of T-DXd treatment. Heterogeneity index, SUVmax, SUVmean and other uptake values were collected to investigate the association with efficacy of T-DXd.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-23
• Study First Submitted QC: 2025-01-23
• Last Update Submitted: 2025-01-23
• Study First Posted: 2025-01-28
• Last Update Posted: 2025-01-28
• Study Start: 2025-02-15
• Primary Completion: 2027-01-15
• Study Completion: 2027-04-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 50

Inclusion Criteria

1. Patients aged over 18 years old.
2. ECOG 0-2.
3. Patients have been diagnosed with unresectable, locally advanced or metastatic HER2-positive breast cancer, which were by means of immunohistochemical analysis (with 3+ indicating positive status), fluorescence in situ hybridization (with an amplification ratio ≥2.0 indicating positive status), or both.
4. Brain metastasis was confirmed by MRI; measurable disease as defined by at least one intracranial cerebral metastatic lesion with diameter ≥ 1.0 cm not previously treated with radiation.
5. It is allowed to use mannitol, bevacizumab, or corticosteroids before enrollment, but dose should be stable for at least one week.
6. Plan to receive Trastuzumab deruxtecan (T-DXd).
7. Adequate bone marrow, liver, kidney and cardiac function.
8. All patients can provide an informed consent before enrolment and data collection.

Exclusion Criteria

1. Leptomeningeal involvement.
2. Uncontrolled large amount of pleural effusion and ascites.
3. Previous treatment of T-DXd.
4. Adequate treatment washout period before enrollment, defined as: major surgery ≥4 weeks, radiation therapy ≥4 weeks, chemotherapy ≥4 weeks, small-molecule targeted agents, anticancer hormonal therapy, antibody-based treatment ≥3 weeks.
5. Patients with previous interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis require corticosteroids treatment; or any clinically active interstitial lung disease currently.
6. Use of any investigational agent within 14 d before initiation of treatment.
7. Concomitant other anticancer therapy, including cytotoxic, targeted agents, immunotherapy, antibody, retinoid or anticancer hormonal treatment.
8. History of malignancy other than squamous cell carcinoma, basal cell carcinoma of the skin or carcinoma in situ of the cervix within the last 3 years, including contralateral breast cancer.
9. Clinically significant cardiac disease.
10. Patients with known hypersensitivity to trastuzumab or 68Ga-FAPI.
11. a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs.
12. Patients with the history of immunodeficiency, including HIV, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation.
13. Patients with HBsAg positive and HBV >=1000, HCV antibody positive, TP-Ab positive or HIV positive.
14. Pregnant or lactating women. Women with childbearing potential must have a negative pregnancy test at screening; also excluded are women with childbearing potential, including women whose last menstrual period was <1 year before screening, unable or unwilling to use adequate contraception from study start to 1 year after the last dose of protocol therapy. Acceptable contraception methods included the application of an intrauterine device, barrier method or total abstinence.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Trastuzumab deruxtecan (T-DXd)	Trastuzumab deruxtecan (T-DXd)	Trastuzumab deruxtecan (T-DXd)

Primary Outcome Measures

Name	Time	Method
Difference of baseline heterogeneity index	6 weeks	Difference of baseline heterogeneity index evaluated by 68Ga-FAPI PET-CT between cerebral lesions reaching ORR or not with the T-DXd treatment.

Secondary Outcome Measures

Name	Time	Method
68Ga-FAPI PET-CT value	6 weeks	68Ga-FAPI PET-CT value changes (heterogeneity index, SUVmax, SUVmean ) at baseline and 2 cycles after T-DXd treatment of whole body metastasis lesions.
Difference of baseline heterogeneity index	6 weeks	Difference of baseline heterogeneity index, SUVmax and SUVmean evaluated by 68Ga-FAPI PET-CT between active or stable brain metastasis.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, Shanghai, China