Clinical trial NCT06225505: Early Detection of Triple Negative Breast Cancer Relapse
Official title: Early Detection of Triple Negative Breast Cancer Relapse: a Clinical Utility Phase II Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Triple Negative Breast Cancer
Keywords: Triple negative breast cancer
68Ga-FAPI-46
ctDNA
Lead sponsor: Institut Curie
Sponsor class: OTHER
Collaborators: name: National Research Agency, France
name: Roche Pharma AG
First posted: 2024-01-26
Enrollment: 450
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: DIAGNOSTIC

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 \~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.

Detailed 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Overall survival
timeFrame: 24 months
Secondary outcomes:
measure: Number of metastatic sites at the time of the clinical/radiological relapse.
timeFrame: Clinical/radiological relapse up to 24 months
measure: Recurrence-free survival
timeFrame: Clinical/radiological relapse up to 24 months
measure: Overall response rate
timeFrame: 12 months
measure: Overal Survival
timeFrame: Up to 24 months
measure: Performance Status Scale
timeFrame: Clinical/radiological relapse up to 24 months
measure: EORTC Core Quality of Life questionnaire (EORTC-QLQ-C30) with the QLQ-BR45 module
timeFrame: Clinical/radiological relapse up to 24 months
measure: 5-level EQ-5D version (EQ-5D-5L)
timeFrame: Clinical/radiological relapse up to 24 months
Other outcomes:
Locations:
city: Avignon
country: France
facility: Sainte-Catherine Institut du Caner Avignon-Provence
city: Bordeaux
country: France
facility: Institut Bergonié
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Lyon
country: France
facility: Centre Leon Bérard
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Montpellier
country: France
facility: Institut du cancer de Montpellier
city: Nîmes
country: France
facility: CHU Nîmes
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Paris
country: France
facility: Hôpital Tenon
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Saint-Cloud
country: France
facility: Institut Curie
city: Toulouse
country: France
facility: ONCOPOLE Claudius Regaud
city: Vandœuvre-lès-Nancy
country: France
facility: Institut de cancérologie de Lorraine
Study officials:
affiliation: Institut Curie
name: François-Clément BIDARD
role: PRINCIPAL_INVESTIGATOR
References: