NCT06225505

Brief Summary

CUPCAKE is a randomized, non-comparative, multicenter, proof-of-concept phase II trial, using the Trials within Cohorts concept(1) to assess the clinical utility of ctDNA monitoring combined with 68Ga-FAPI-46-PET-CT imaging upon ctDNA detection for the surveillance of patients with a non-metastatic TNBC at high risk of relapse. The study has two steps. In Step 1, patients who have completed the treatments for a localized TNBC will undergo ctDNA monitoring every \~4 months (± 2 weeks). In Step 2, patients for whom ctDNA will be detected will then be randomized between an observation arm, in which monitoring will continue until the detection of a clinical relapse, and an experimental arm, in which the ctDNA detection will be revealed to both the patient and the clinician: patients will then undergo a 18F-FDG PET-CT and a 68Ga-FAPI-46-PET-CT, in addition to whatever workup the investigator will deem necessary.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
450

participants targeted

Target at P75+ for not_applicable

Timeline
64mo left

Started Jan 2026

Longer than P75 for not_applicable

Geographic Reach
1 country

13 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress6%
Jan 2026Aug 2031

First Submitted

Initial submission to the registry

December 12, 2023

Completed
2 months until next milestone

First Posted

Study publicly available on registry

January 26, 2024

Completed
1.9 years until next milestone

Study Start

First participant enrolled

January 5, 2026

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 3, 2031

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 3, 2031

Last Updated

January 22, 2026

Status Verified

January 1, 2026

Enrollment Period

5.6 years

First QC Date

December 12, 2023

Last Update Submit

January 20, 2026

Conditions

Keywords

Triple negative breast cancer68Ga-FAPI-46ctDNA

Outcome Measures

Primary Outcomes (1)

  • Overall survival

    OS rate for the main analysis (primary endpoint) is defined as the percentage of patients still alive 36 months after the randomization. If the patient is not present at the 36th month visit, survival data may be obtained by other means, such as telephone contact with the patient, his family, his current physician, or consulting local death registries. A non-comparative analysis will be conducted in the experimental arm, and the control arm will serve as reference.

    36 months

Secondary Outcomes (8)

  • Number of metastatic sites at the time of the clinical/radiological relapse.

    Clinical/radiological relapse up to 36 months

  • Recurrence-free survival

    Clinical/radiological relapse up to 36 months

  • Overall response rate

    12 months

  • Overal Survival

    Up to 36 months

  • Performance Status Scale

    Clinical/radiological relapse up to 36 months

  • +3 more secondary outcomes

Study Arms (2)

Experimental arm

EXPERIMENTAL

In the experimental arm, patients and their treating physician will be made aware of the molecular relapse (positive ctDNA detection results) in study steps 1 (ctDNA monitoring). To locate metastatic deposits, patients will be offered to undergo a whole-body imaging with 18F-FDG PET-CT and 68Ga-FAPI-46-PET-CT, in addition to any other workup considered as relevant by their treating physician.

Diagnostic Test: ctDNA monitoringDiagnostic Test: 68Ga-FAPI-46-PET-CT

Control arm

SHAM COMPARATOR

In the control arm, patients and their treating physician will not be made aware of the molecular relapse and will continue the standard surveillance with repeated ctDNA test every 4 months (blinded). ). At the time of the clinical/radiological diagnosis of relapse, similar procedures will be performed (18F-FDG PET-CT, 68Ga-FAPI-46-PET-CT, and tumor genetic landscape assessment by ctDNA analysis).

Diagnostic Test: ctDNA monitoringDiagnostic Test: 68Ga-FAPI-46-PET-CT

Interventions

ctDNA monitoringDIAGNOSTIC_TEST

For each patient included, a ctDNA detection assay will be performed in blood samples every 4 months, while extra-plasma will be banked. ctDNA results will be available with a turnaround time of less than 3 weeks. When negative, ctDNA detection results will not be disclosed to patients nor clinicians.

Control armExperimental arm
68Ga-FAPI-46-PET-CTDIAGNOSTIC_TEST

). To locate metastatic deposits, patients will be offered to undergo a whole-body imaging with 18F-FDG PET-CT and 68Ga-FAPI-46-PET-CT, in addition to any other workup considered as relevant by their treating physician.

Control armExperimental arm

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must be female ≥ 18 years old
  • Patients diagnosed with a non-metastatic TNBC (ER \& PR \<10%, HER2- per ASCO/CAP guidelines). Patients must have been previously evaluated by a 18F-FDG PET-CT or a bone scintigraphy combined with a thorax, abdomen and pelvis CT scan with contrast
  • High-risk primary tumor, defined as:
  • Lack of pathological complete response after neoadjuvant chemotherapy (RCB I, II or III; RCB I being capped to a maximum of 30% of included patients) OR, in the absence of neoadjuvant chemotherapy,
  • Stage IIB-III (i.e., T2N1, any T3-T4, any N2-3) OR
  • Any loco-regional relapse occurring after a prior ipsilateral, curatively treated TNBC
  • No sign of local or distant relapse, as per investigator assessment
  • Performance status \< 2
  • Available FFPE tumor block with \> 10% cellularity or 11 tumor sections with \>10% cellularity
  • Patient able to comply with protocol requirements
  • Patients covered by a health insurance

You may not qualify if:

  • Any uncontrolled disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding or any other medical condition that, in the opinion of the investigator, interferes with the trial procedures
  • Male participants
  • Patients with altered mental status or psychiatric disorder that, in the opinion of the investigator, would preclude a valid patient informed consent.
  • Patients who have difficulty undergoing trial procedures for geographic, social or psychological reasons
  • Person deprived of liberty or under guardianship
  • History of another primary malignancy except for the following :
  • Basal cell carcinoma or any in situ carcinoma treated with curative intent
  • Any stage I-II malignancy treated with curative intent with no evidence of active disease in the last five years
  • For step #2 (randomization after ctDNA detection): clinical/radiological metastatic relapse before the detection of the molecular relapse.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

Sainte-Catherine Institut du Caner Avignon-Provence

Avignon, 84918, France

NOT YET RECRUITING

Institut Bergonié

Bordeaux, 33000, France

NOT YET RECRUITING

Centre Jean Perrin

Clermont-Ferrand, 63011, France

NOT YET RECRUITING

Centre Leon Bérard

Lyon, 69008, France

NOT YET RECRUITING

Institut Paoli-Calmettes

Marseille, 13009, France

NOT YET RECRUITING

Institut du cancer de Montpellier

Montpellier, 34298, France

NOT YET RECRUITING

CHU Nîmes

Nîmes, 30900, France

NOT YET RECRUITING

Hôpital Saint-Louis

Paris, 75010, France

NOT YET RECRUITING

Hôpital Tenon

Paris, 75020, France

NOT YET RECRUITING

Centre Eugène Marquis

Rennes, 35000, France

NOT YET RECRUITING

Institut Curie

Saint-Cloud, 92340, France

RECRUITING

ONCOPOLE Claudius Regaud

Toulouse, 31059, France

NOT YET RECRUITING

Institut de cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

NOT YET RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast NeoplasmsNeoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • François-Clément BIDARD

    Institut Curie

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne-Claire COYNE

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Masking Details
Upon detection of ctDNA during Step1, patients will be centrally assigned to the control or the experimental arm (1:1) using the eCRF. Randomization will be stratified by RCB score (I/II vs. III/NA because no neoadjuvant chemotherapy) and by time to molecular relapse (\< 12 months vs. ≥ 12 months between surgery and molecular relapse).
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Model Details: CUPCAKE is a randomized, non-comparative, multicenter, proof-of-concept phase II trial, using the Trials within Cohorts concept to assess the clinical utility of ctDNA monitoring combined with 68Ga-FAPI-46-PET-CT imaging upon ctDNA detection for the surveillance of patients with a non-metastatic TNBC at high risk of relapse. 68Ga-FAPI-46 is the radiopharmaceutical product. There is no study treatment (standard of Care).
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 12, 2023

First Posted

January 26, 2024

Study Start

January 5, 2026

Primary Completion (Estimated)

August 3, 2031

Study Completion (Estimated)

August 3, 2031

Last Updated

January 22, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

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.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
Data requests can be submitted starting 9 months after article publication and will be made accessible for up to 12 months.
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).

Locations