OptimICE-PCR: De-Escalation of Therapy in Early-Stage TNBC Patients Who Achieve pCR After Neoadjuvant Chemotherapy with Checkpoint Inhibitor Therapy
Categories (click each to see list of all clinical trials associated with that category): Breast (ONC)
Current Status: Not open
Phase: III (Cancer Control)
Principal Investigator: Krishnamurthy, Jairam
Eligibility: https://clinicaltrials.gov/study/NCT05812807?term=NCT05812807&rank=1
Summary
2.1 Primary objective
To evaluate whether observation results in a non-inferior RFS compared to adjuvant pembrolizumab in early-stage TNBC patients who achieve a pCR after neoadjuvant chemotherapy with pembrolizumab.
Hypothesis: Patients with clinical stage II-III TNBC who achieve a pCR after neoadjuvant chemotherapy with immune checkpoint inhibitor (ICI) therapy and who are observed without additional adjuvant systemic therapy will not have inferior RFS compared to patients who receive 27 weeks of adjuvant pembrolizumab. This will be designed as a de-escalation study, with a 3-year RFS rate of 94% estimated in the pembrolizumab arm and non-inferiority of the observation arm declared if the 3-year RFS rate is 91% or higher.
2.2 Secondary objectives
To evaluate whether observation compared to adjuvant pembrolizumab impacts the following:
2.2.1 RFS by stage at presentation and by receipt of prior anthracycline therapy
2.2.2 Adverse event rate: difference in Grade 3 or higher adverse event rates overall and Grade 3 or higher irAE rates
2.2.3 Overall Survival (OS)
2.2.4 Locoregional recurrence (LRR, both isolated LRR as first events and LRR events simultaneous with DM)
2.2.5 RFS, LRR, OS, adverse events, and QOL by age (≤45, 46-65, and >65), race, and ethnicity
2.2.6 Adverse events related to receipt of radiotherapy (as defined in Section 13.4)
2.3 Quality of Life and Patient-Reported Outcomes Objectives
2.3.1 Quality of Life - Primary objective
To compare quality of life (QOL) at approximately 27 weeks as assessed by the FACT-B Trial Outcome Index between patients randomized to adjuvant pembrolizumab versus observation.
2.3.2 Quality of Life - Exploratory objectives
- To describe trajectories of QOL over time among patients randomized to adjuvant pembrolizumab vs. observation
- To compare various QOL domains after approximately 27 weeks as assessed by the 5 subscales of the FACT-B Index between patients randomized to adjuvant pembrolizumab versus observation.
- To compare self-reported symptomatic adverse events as outlined in section 14.1.1 at approximately 27 weeks assessed by the PRO-CTCAE between patients randomized to adjuvant pembrolizumab versus observation.
2.3.3 Value of Care - Primary objective
To assess the social value of de-escalation of adjuvant breast cancer immunotherapy at approximately 27 weeks and, by modelling, over a lifetime.
2.3.4 Value of Care - Secondary objectives
- To assess the value of de-escalation of breast cancer immunotherapy from the payer perspective at approximately 27 weeks and, by modelling, over a lifetime.
- To compare patient out-of-pocket costs at approximately 27 weeks between patients randomized to adjuvant pembrolizumab versus observation.
- To compare financial toxicity at approximately 27 weeks between patients randomized to adjuvant pembrolizumab versus observation.
- To compare work/productivity impairment at approximately 27 weeks between patients randomized to adjuvant pembrolizumab versus observation.
2.3.5 Value of Care - Exploratory objectives
- To describe trajectories of financial toxicity and work/productivity impairment over time from baseline to approximately 27 weeks among patients randomized to adjuvant pembrolizumab versus observation.
- To develop and assess a measure of value from the patient perspective at approximately 27 weeks. This measure, to be developed in collaboration with a patient advocate, will combine both costs and outcomes, and incorporate patient out-of-pocket costs and financial toxicity.