The purpose of this research study is to look at the efficacy (the effect on tumor) and the safety (the effect on body) of the study drugs when given as a combination in patients with metastatic recurrent epidermal growth factor receptor 2 (HER2) negative inflammatory breast cancer. This is a phase II study of 2 drugs used in combination: nivolumab and ipilimumab. The combination of these drugs is already approved by the Food and Drug Administration (FDA) to treat advanced melanoma (a type of skin cancer). Nivolumab and ipilimumab are not approved by the FDA for patients with metastatic recurrent HER2 negative inflammatory breast cancer, hence the treatment is considered experimental or investigational.
PRIMARY OBJECTIVES: I. To determine progression free survival (PFS) in patients with newly recurrent HER2 negative inflammatory breast cancer (IBC) treated with nivolumab and ipilimumab according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. SECONDARY OBJECTIVES: I. To assess the overall response rate (ORR) and clinical benefit rate (CBR) according to RECIST criteria v1.1, in patients with recurrent IBC treated with nivolumab and ipilimumab. II. To assess overall survival in patients with recurrent HER2 negative IBC treated with nivolumab and ipilimumab. III. To assess the safety and tolerability of nivolumab and ipilimumab in patients with recurrent IBC according to the National Cancer Institute Common Terminology Criteria for Adverse Events v 4.03. TERTIARY OBJECTIVES: I. To assess the predictive value of baseline iSCORE and programmed cell death 1 ligand 1 (PDL-1) expression using archival tissue samples as well as any standard of care tissue obtained during study treatment. II. To assess the predictive value of circulating cell-free tumor DNA (ctDNA) and immune signature by exosome analysis using blood samples at baseline. OUTLINE: Patients receive nivolumab intravenously (IV) over 30 minutes every 2 weeks (Q2W) and ipilimumab IV over 90 minutes every 6 weeks (Q6W) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 4 weeks for 12 weeks, and then every 3 months for up to 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Northwestern University
Chicago, Illinois, United States
Progression Free Survival (PFS)
PFS in patients with newly recurrent HER2 negative IBC treated with nivolumab and ipilimumab as evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 assessed from the date of first study treatment to the date of disease progression or death from any cause, assessed up to 2 years.
Time frame: Up to 2 years
Overall Response Rate (ORR)
Evaluate the ORR according to RECIST criteria v1.1 in patients with recurrent Inflammatory Breast Cancer (IBC) treated with nivolumab and ipilimumab. ORR will be the number of patients with complete response plus the number of patients with partial response. Patients will have imaging scans every 12 weeks assessed up to 2 years. In general: Complete Response (CR): Disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Every 12 weeks from treatment initiation for up to 2 years. Range of cycles patients completed 1-3 cycles (1 cycle =12 weeks)
Clinical Benefit Rate (CBR)
Evaluate the CBR according to RECIST criteria v1.1 in patients with recurrent Inflammatory Breast Cancer (IBC) treated with nivolumab and ipilimumab. CBR will be the number of patients with complete response plus the number of patients with partial response plus those with stable disease. Patients will have imaging scans every 12 weeks assessed up to 2 years. In general: Complete Response (CR): Disappearance of all target and non target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: Every 12 weeks from treatment initiation for up to 2 years. Range of cycles patients completed 1-3 cycles (1 cycle =12 weeks)
Overall Survival (OS)
To assess overall survival in patients with recurrent HER2 negative IBC treated with nivolumab and ipilimumab, patients will be followed from the start of treatment until 2 years post-treatment or death, whichever occurs first, and average survival time will be measured.
Time frame: Up to 2 years
Number of Adverse Events of Nivolumab and Ipilimumab Combination Treatment
Assess the safety and tolerability of nivolumab and ipilimumab in patients with recurrent Inflammatory Breast Cancer (IBC) by measuring the number, frequency, and severity of adverse events according to the National Cancer Institute Common Terminology Criteria Adverse events (CTCAE) v 4.03. AEs that were determined to be at least possibly related to study drug and grade 3-5 are reported. In general grading is as follows: Grade 1 - mild Grade 2 - moderate Grade 3 - severe Grade 4 - life threatening Grade 5 - fatal
Time frame: From the initiation of treatment until 12 weeks after study discontinuation. Range of cycles completed by patients 1-3 (1 cycle =12weeks)
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