Early Detection of Triple Negative Breast Cancer Relapse

Triple Negative Breast Cancer Clinical Trial

— CUPCAKE  

Official title:

Early Detection of Triple Negative Breast Cancer Relapse: a Clinical Utility Phase II Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06225505
• Other study ID #: IC 2022-02_CUPCAKE
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 30, 2024
• Est. completion date: December 15, 2028

Study information

• Verified date: May 2024
• Source: Institut Curie
• Contact: Sandra B NESPOULOUS
• Phone: 0147111654
• Email: drci.promotion[@]curie.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 ~3 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.

Description:

The CUPCAKE trial will follow the Trials within Cohorts (TwiCs) approach. Non-metastatic TNBC patients at high risk of relapse will be included, after having signed a written informed consent, in a cohort allowing them to be followed by ctDNA monitoring every 3 months. For each patient included, a ctDNA detection assay will be performed in blood samples every 3 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. First line therapy will not be started until a metastatic relapse has been found by imagining: no treatment will be started in the sole basis of a positive ctDNA test. If, at any timepoint, ctDNA is detected (molecular relapse), patients will be randomized in a 1:1 ratio. - In the experimental arm, patients and their treating physician will be made aware of the molecular relapse (positive ctDNA detection results). 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. If/when a clinical/radiological relapse is observed, the patient performance status will be registered (secondary objective) and systemic or local treatments will be decided by physicians. These treatments could be informed by the genetic landscape of the relapse, assessed by ctDNA. - 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 3 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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 450
• Est. completion date: December 15, 2028
• Est. primary completion date: December 15, 2026
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients must have signed a written informed consent before inclusion

2. Patients must be female = 18 years old

3. 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

4. Patients who have undergone surgery with curative intent for their non-metastatic TNBC. Surgery must have been performed between 1 to 18 months before inclusion. Patients must have initiated their adjuvant therapy, whenever indicated, since at least 4 weeks. For patients receiving an experimental adjuvant treatment in a clinical trial, any intervention planned as part of this trial must be completed before inclusion.

5. High-risk primary tumor, defined as:

1. 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,

2. Stage IIB-III (i.e., T2N1, any T3-T4, any N2-3) OR

3. Any loco-regional relapse occurring after a prior ipsilateral, curatively treated TNBC

6. No sign of local or distant relapse, as per investigator assessment

7. Performance status < 2

8. Available FFPE tumor block with > 10% cellularity or 11 tumor sections with >10% cellularity

9. Patient able to comply with protocol requirements

10. Patients covered by a health insurance

Exclusion Criteria:

1. 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

2. Male participants

3. Patients with altered mental status or psychiatric disorder that, in the opinion of the investigator, would preclude a valid patient informed consent.

4. Patients who have difficulty undergoing trial procedures for geographic, social or psychological reasons

5. Person deprived of liberty or under guardianship

6. History of another primary malignancy except for the following :

1. Basal cell carcinoma or any in situ carcinoma treated with curative intent

2. Any stage I-II malignancy treated with curative intent with no evidence of active disease in the last five years

7. For step #2 (randomization after ctDNA detection): clinical/radiological metastatic relapse before the detection of the molecular relapse.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

Intervention

Diagnostic Test:
• ctDNA monitoring
For each patient included, a ctDNA detection assay will be performed in blood samples every 3 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.
• 68Ga-FAPI-46-PET-CT
). 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.

Locations

Country	Name	City	State
France	Sainte-Catherine Institut du Caner Avignon-Provence	Avignon
France	Institut Bergonié	Bordeaux
France	Centre Jean Perrin	Clermont-Ferrand
France	Centre Leon Bérard	Lyon
France	Institut Paoli-Calmettes	Marseille
France	Institut du cancer de Montpellier	Montpellier
France	CHU Nîmes	Nîmes
France	Hôpital Saint-Louis	Paris
France	Hôpital Tenon	Paris
France	Centre Eugène Marquis	Rennes
France	Institut Curie	Saint-Cloud
France	ONCOPOLE Claudius Regaud	Toulouse
France	Institut de cancérologie de Lorraine	Vandœuvre-lès-Nancy

Sponsors (3)

Lead Sponsor	Collaborator
Institut Curie	National Research Agency, France, Roche Pharma AG

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival	OS rate for the main analysis (primary endpoint) is defined as the percentage of patients still alive 24 months after the randomization. If the patient is not present at the 24th 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.	24 months
Secondary	Number of metastatic sites at the time of the clinical/radiological relapse.	The number of metastatic sites upon clinical/radiological relapse will be defined post-hoc by the Adjudication Committee as the number of organs or systems in which metastases are detected at the time of the clinical/radiological relapse, among the following propositions: lymph nodes, bones, liver, lungs, central nervous system/meninges, peritoneum, others.	Clinical/radiological relapse up to 24 months
Secondary	Recurrence-free survival	RFS [recurrence-free survival], defined as the time from randomization to clinical/radiological relapse or death; PFS [progression-free survival], defined as the time from randomization to the first progression or death occurring after clinical/radiological relapse; 1L-PFS [first line PFS], defined as the time from clinical/radiological relapse to first progression or death ; 2L-PFS [second line PFS], defined as the time from first to second progression or death; progression being defined per RECIST criteria.	Clinical/radiological relapse up to 24 months
Secondary	Overall response rate	Best ORR is defined as the proportion of patients with a complete response (CR) or partial response (PR) based on local investigator assessment according to RECIST 1.1, until first progression or last tumor assessment in the absence of progression. ORR will be reported with its 95% confidence interval by arm.	12 months
Secondary	Overal Survival	Overall Survival is defined as the time between randomization and death.	Up to 24 months
Secondary	Performance Status Scale	Proportion of patients presenting with an altered general condition (PS =2) at first evidence of clinical or radiological relapse.; The population of interest consists in randomized patients.	Clinical/radiological relapse up to 24 months
Secondary	EORTC Core Quality of Life questionnaire (EORTC-QLQ-C30) with the QLQ-BR45 module	The EORTC-QLQ-C30 questionnaire with the QLQ-BR45 is used to report health-related QoL in all included patients. Summary statistics of the scores for all functional/symptom scales will be calculated at each assessment time point, according to the scoring procedure recommended by the EORTC.; All of the scales and single item measures range in score from 0 to 100. A high score for the functional scales and functional single items represents a high/healthy level of functioning, whereas a high score for the symptom scales and symptom item represents a high level of symptomatology or problems.	Clinical/radiological relapse up to 24 months
Secondary	5-level EQ-5D version (EQ-5D-5L)	y. Each state is referred to in terms of a 5 digit code. For example, state 11111 indicates no problems on any of the 5 dimensions, while state 12345 indicates no problems with mobility, slight problems with washing or dressing, moderate problems with doing usual activities, severe pain or discomfort and extreme anxiety or depression. A completely healthy patient would have a score of 11111. This 5-digit number can be converted into a score using a special algorithm that is not publicly available. This point value is called the EQ-5D-5L Index and represents the patient's health status.	Clinical/radiological relapse up to 24 months