Early detection of triple negative breast cancer relapse (CUPCAKE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Curie, Institut Curie

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01]

Decision date (initial)

2023-05-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ANR - RHU CASSIOPEIA · ROCHE

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Others

To evaluate the efficacy of ctDNA-based surveillance strategy, in terms of risk of early death

Secondary objectives 11

1. To evaluate the efficacy of the surveillance strategy, using other endpoints
2. To evaluate the efficacy of the surveillance strategy, in terms of prevalence of patient with an altered general condition at relapse
3. To evaluate the safety of the ctDNA and 68Ga-FAPI-46 PET-CT monitoring process
4. To evaluate the impact of the surveillance process on patient-reported outcomes
5. To evaluate the outcomes in patients who presented with a clinical/radiological relapse at the time of/before any ctDNA detection
6. Exploratory: To explore the feasibility of the surveillance process
7. Exploratory: To evaluate the diagnostic performances of the 68Ga-FAPI-46 PET-CT
8. Exploratory: To explore the association between patients’ characteristics and outcomes
9. Exploratory: To explore ctDNA kinetics upon treatment start after clinical/radiological relapse
10. Exploratory: To better characterize the cancer biology of patients with an early TNBC relapse
11. Exploratory: To explore the medico-economic correlates of the surveillance strategy procedure

Conditions and MedDRA coding

Triple-negative breast cancer (TNBC) patients at high risk of relapse

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

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: a.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, b.Stage IIB-III (i.e., T2N1, any T3-T4, any N2-3) OR c. 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 7

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 : a. Basal cell carcinoma or any in situ carcinoma treated with curative intent b. Any stage I-II malignancy treated with curative intent with no evidence of active disease in the last five years 6.7. For step #2 (randomization after ctDNA detection): clinical/radiological
7. For step #2 (randomization after ctDNA detection): clinical/radiological metastatic relapse before the detection of the molecular relapse

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival rate 24 months after the randomization. The population of interest consists in randomized patients. A non-comparative analysis will be conducted in the experimental arm, and the control arm will serve as reference

Secondary endpoints 11

1. Number of metastatic sites at the time of the clinical/radiological relapse; b. RFS [recurrence-free survival]; PFS [progression-free survival]; 1L-PFS [first line PFS]; 2L-PFS [second line PFS]; progression being defined per RECIST criteria.; c. Best ORR [overall response rate] ; OS (not limited to the first 24 months), measured from randomization.
2. 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.
3. AEs and SAEs, considered by the investigator as related to either ctDNA analysis or 68Ga-FAPI-46 PET-CT, reported by rate and grade (NCI CTC-AEs v5.0). The population of interest consists in all included patients
4. QLQ-C30 QoL questionnaire with the QLQ-BR45 module will be filled at inclusion, upon molecular relapse in the experimental arm, upon radiological/clinical relapse in the standard arm, and during post-relapse follow-up. Populations of interest consist in (i) all included patients and (ii) patients who have experienced a molecular relapse and/or a clinical/radiological relapse.
5. Proportion of patients presenting with an altered general condition (performance status ≥2) upon clinical/radiological relapse; b. Overall Survival measured from clinical/radiological relapse The population of interest consists in patients who presented with a clinical/radiological relapse at the time of/before any ctDNA detection.
6. Exploratory: a. Rate of ctDNA analysis technical failures; b. ctDNA analysis turnaround time; c. Rate of 68Ga-FAPI PET-CT technical failures; c/ Rate of 68Ga-FAPI-46 PET-CT technical failures, defined as results being not available because of a technical issue with the scanner or the gamma-camera, an insufficient quality of the radiotracer or of the images generated. d/ Reasons for patient non-adherence to either ctDNA analysis and/or 68Ga-FAPI-46 PET-CT will be registered.
7. Exploratory: 1/ Rate of patients with ctDNA detected and with tumor deposits detected with 68Ga-FAPI-46 PET-CT: 2/ Comparison of 68Ga-FAPI-46 PET-CT with the rest of the imaging procedures in terms of: a/ Rate of patients with tumor deposits detected; b/ Number of metastases identified in each organ/system
8. Exploratory: Associations between quantitative/qualitative results of the primary tumor genomic landscape, digital pathology features, ctDNA detection, 68Ga-FAPI-46 PET-CT results, patients’ characteristics and outcomes.
9. Exploratory: Quantitative changes in ctDNA levels three, six and nine months after treatment start, in relapsed patients.
10. Exploratory: Supplemental molecular analyses will be performed on banked plasma and optional biopsies (fresh and frozen) performed at relapse ; available tissue sections will be centralized at the end of the study for additional image analyses, to explore potential
11. Exploratory: Cost-effectiveness analysis of 68Ga-FAPI-46 PET-CT + ctDNA compared to the existing surveillance strategies.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Curie

Sponsor organisation

Institut Curie

Address

26 Rue D Ulm

City

Paris

Postcode

75005

Country

France

Scientific contact point

Organisation

Institut Curie

Contact name

François-Clément Bidard

Public contact point

Organisation

Institut Curie

Contact name

François-Clément Bidard

Institut Curie

Sponsor organisation

Institut Curie

Address

26 Rue D Ulm

City

Paris

Postcode

75005

Country

France

Scientific contact point

Organisation

Institut Curie

Contact name

Véronique Gillon

Public contact point

Organisation

Institut Curie

Contact name

Véronique Gillon

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications