To evaluate the clinical benefit of a post-operative adjuvant therapy combining radiotherapy + Nivolumab + Ipilimumab versus radiotherapy + Capecitabine in Triple Negative Breast Cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy.
This trial is an open-label, randomised, multicentric, comparative, Phase II study aiming to evaluate the clinical benefit of a combined treatment associating radiotherapy + Nivolumab + Ipilimumab versus radiotherapy + Capecitabine (standard treatment) in early TNBC patients who have Residual cancer burden (RCB) II or III residual disease after neoadjuvant chemotherapy. Following validation of eligibility criteria, patients will be randomised (1:1) to receive: * Arm A: Nivolumab (360 mg IV, every 3 weeks) for 8 doses and Ipilimumab (1 mg/kg, IV, every 6 weeks or every 2 doses of Nivolumab in case of dose delays) for 4 doses. * Arm B: Capecitabine (1000 mg/m2 twice a day, Bis In Die \[BID\]), 14 days on / 7 days off for 8 cycles. In both arms, radiotherapy will be administered as per standard practice and has to be initiated one week before C1D1.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
95
Radiotherapy will be maintained in each Arm.
Radiotherapy will be maintained in each Arm.
Radiotherapy will be maintained in each Arm.
Institut de Cancérologie de l'Ouest
Angers, France
Institut Sainte Catherine
Avignon, France
CHRU Besançon
Besançon, France
Disease free survival (DFS)
DFS is defined as the time from randomization until the date of the first relapse (local/regional recurrence or distant metastasis) or death (from any cause) whichever comes firsts and regardless of whether the patient withdraws from randomised study treatment or receives another anti-cancer therapy prior to disease relapse.
Time frame: At 2 years
Overall survival
Overall survival will be measured from the date of randomization to the date of death from any cause.
Time frame: Up to 2 years
Local-regional recurrence
Local-regional recurrence (LRR) refers to relapse of the primary tumor site
Time frame: Up to 2 years
Distant metastasis
Distant metastasis is defined as presence of any non-local metastatic sites.
Time frame: Up to 2 years
Disease recurrence/relapse (local or distant)
Rate of patients with recurrence at 1 year and 2 year post-randomisation as well as time to recurrence will be analysed.
Time frame: Up to 2 years
Adverse Event
The assessment of safety will be based mainly on the frequency of adverse events based on the common toxicity criteria (CTCAE-V5.0) grade.
Time frame: Up to 2 years
EORTC QLQ C30
Patient reported outcomes and quality of life will be assessed using the validated following questionnaire: The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C30). The QLQ-C30 incorporates nine multi-item scales: five functional scales (physical, role, cognitive, emotional, and social); three symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality-of-life scale. Several single-item symptom measures are also included. See scoring manual at :https://www.eortc.be/qol/files/SCManualQLQ-C30.pdf.
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Centre Francois Baclesse
Caen, France
Centre d'Oncologie Radiothérapie 37
Chambray-lès-Tours, France
Hopital Prive Jean Mermoz
Lyon, France
Centre Léon Bérard
Lyon, France
Clinique de la Sauvegarde
Lyon, France
Institut Paoli Calmettes
Marseille, France
Centre Antoine Lacassagne
Nice, France
...and 7 more locations
Time frame: At Baseline, every 12 weeks and 30 days after the last dose
Questionnaire EORTC QLQ BR-23
Patient reported outcomes and quality of life will be assessed using the validated following questionnaire :The European Organization for Research and Treatment of Cancer Breast-Cancer-Specific Quality of Life Questionnaire. See details at :https://www.eortc.be.
Time frame: At Baseline, every 12 weeks and 30 days after the last dose
Questionnaire EORTC QLQ FA-12 Fatigue
Patient reported outcomes and quality of life will be assessed using the validated following questionnaire : EORTC QLQ FA-12 Fatigue. The European Organisation for Research and Treatment of Cancer (EORTC) Group has developed a multidimensional instrument measuring cancer-related fatigue to be used in conjunction with the quality of life core questionnaire (EORTC QLQ-C30). The module EORTC QLQ-FA12 assesses physical, cognitive, and emotional aspects of cancer-related fatigue. See details at :https://www.eortc.be.
Time frame: At Baseline, every 12 weeks and 30 days after the last dose
Questionnaire patient self-rating mood scale.
Patient reported outcomes and quality of life will be assessed using the following questionnaire : patient self-rating mood scale.
Time frame: At Baseline, every 12 weeks and 30 days after the last dose
Mutational profiles
To define the molecular characteristics of the tumor' patients: Mutational profiles of tumors (Whole Exome seq,)
Time frame: At Baseline and in case of disease relapse up to 2 years
Copy Number alterations.
To define the molecular characteristics of the tumor' patients: Copy Number alterations.
Time frame: At Baseline and in case of disease relapse up to 2 years
Loss of heterozygosity.
To define the molecular characteristics of the tumor' patients: loss of heterozygosity.
Time frame: At Baseline and in case of disease relapse up to 2 years
Circulating tumor DNA
Circulating tumor DNA detection and analysis will be performed on tumor' patients.
Time frame: At Baseline and in case of disease relapse up to 2 years
Molecular Subtyping
To define Molecular Subtyping of TNBC (RNAseq) on tumor' patients.
Time frame: At Baseline and in case of disease relapse up to 2 years
Immune monitoring
To perform Immune monitoring of circulating immune cells and circulating tumor cells on blood sample.
Time frame: At cycle1 (each cycle is 21 days), cycle 2, cycle 5 and 24 months after randomisation or in case of relapse
Circulating growth factors
To assess levels of circulating growth factors and cytokines on blood sample.
Time frame: At cycle1 (each cycle is 21 days), cycle 2, cycle 5 and 24 months after randomisation or in case of relapse
Cytokines
To assess levels of cytokines on blood sample.
Time frame: At cycle1 (each cycle is 21 days), cycle 2, cycle 5 and 24 months after randomisation or in case of relapse
PDL1
To assess the presence in plasma of soluble PDL1.
Time frame: At cycle1 (each cycle is 21 days), cycle 2, cycle 5 and 24 months after randomisation or in case of relapse
PDL2
To assess the presence in plasma of soluble PDL2.
Time frame: At cycle1 (each cycle is 21 days), cycle 2, cycle 5 and 24 months after randomisation or in case of relapse