68Ga-FAPI-46 PET/CT for Predicting Histological Response in Triple-negative Breast Cancer (FAP-IT) (FAP-IT)

68Ga-FAPI-46 PET/CT for Predicting Histological Response to Neoadjuvant Chemo-immunotherapy in Triple-negative Breast Cancer

Prospective multicenter study evaluating the prediction of histological response after neoadjuvant pembrolizumab in combination with chemotherapy by pre-treatment 68Ga-FAPI-46 PET/CT imaging in patients with early-stage high-risk TNBC.

Study Overview

• Status: Not yet recruiting
• Conditions: Triple Negative Breast Cancer
• Intervention / Treatment: Procedure: 68Ga-FAPI-46 PET/CT imaging

Detailed Description

Prospective multicenter study evaluating the prediction of histological response of pembrolizumab in combination with neoadjuvant chemotherapy by pre-treatment 68Ga-FAPI-46 PET/CT imaging in patients with early-stage high-risk TNBC.

Patients will receive the newly established standard of care of neoadjuvant pembrolizumab 200 mg Q3W given with 4 cycles of paclitaxel + carboplatin, then with 4 cycles of doxorubicin or epirubicin + cyclophosphamide. After definitive surgery, patients will receive adjuvant pembrolizumab for 9 cycles or until recurrence or unacceptable toxicity.

The 68Ga-FAPI-46 PET/CT scan will be performed for each patient pre-therapy and on the same machine as the 18F-FDG PET/CT scan and within 14 days before the start of treatment.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sandra Nespoulous; Phone Number: 0147111654; Email: drci.promotion@curie.fr
• Study Contact Backup: Name: Marie-Emmanuelle LEGRIER; Phone Number: 0156245649; Email: drci.promotion@curie.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female with age ≥ 18 years,
2. Patients with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) for whom a neoadjuvant treatment with chemotherapy + pembrolizumab is the recommended option as standard of care,
3. Patients with measurable targets according to RECIST/PERCIST criteria,
4. Patients without distant metastasis based on staging 18F-FDG PET/CT,
5. Patients with tumor tissue available,
6. Patients who provided a signed written informed consent,
7. Patient ability to comply with protocol requirements,
8. Patients covered by a health insurance system.

Exclusion Criteria:

1. Pregnant and lactating women,
2. Patients with prior anti-PD(L)1 immunotherapy,
3. Patients with any contra-indication to chemo-immunotherapy standard of care therapy, per investigator assessment,
4. Patients with altered mental status or psychiatric disorder that, in the opinion of the investigator, would preclude a valid patient informed consent,
5. Patients who have difficulty undergoing trial procedures for geographic, social or psychological reasons,
6. Patients who are not affiliated to a social security system, or who are deprived of liberty, or under guardianship.
7. Person deprived of liberty or under guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Triple Negative Breast Cancer; Patients with early-stage high-risk Triple Negative Breast Cancer	Procedure: 68Ga-FAPI-46 PET/CT imaging; The 68Ga-FAPI-46 PET/CT scan will be performed for each patient pre-therapy and on the same machine as the 18F-FDG PET/CT scan and within 14 days before the start of treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the ROC curve	To measure the performance of 68Ga-FAPI-46 PET/CT imaging to predict complete histological response after neoadjuvant chemotherapy plus Pembrolizumab, in terms of Area under the ROC curve (AUC of the ROC curve).	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT performances	Detection of metastases (using the total number of metastatic lesion)	Baseline
Comparison of 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT performances	Evaluation of the tumor burden (using the total FAP expression tumor volume/TFTV* and the total metabolic tumor volume/TMTV*, respectively).	Baseline
Comparison of 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT predictive performances	Comparison of 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT predictive performances, separately and combined.	Baseline
Evaluation of predictive model performance combining 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT	Evaluation of predictive model performance combining 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT imaging data, using sensitivity, specificity, positive and negative predictive values and area under the ROC curve (AUC of the ROC curve)	Baseline

Collaborators and Investigators

• Sponsor: Institut Curie
• Investigators: Principal Investigator: Romain-David SEBAN, Institut Curie

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2024
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2027

Study Registration Dates

• First Submitted: March 25, 2024
• First Submitted That Met QC Criteria: April 2, 2024
• First Posted (Actual): April 5, 2024

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; FAPI-46
• Other Study ID Numbers: IC 2022-07; 2023-507860-37-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Investigators will share de-identified data sets with interested researchers, educators or clinicians. Materials generated under the project will be disseminated in accrodance with Institut Curie policies.
• IPD Sharing Time Frame: Data requests can be submitted starting 9 months after article publication and will be made accessible for up to 12 months.
• IPD Sharing Access Criteria: Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific reserach, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No