Pilot Clinical Trial Examining the Safety and Efficacy of Neratinib in Combination With Ruxolitinib in Patients With Chemotherapy-pretreated Metastatic Triple Negative Breast Cancer With Chest Wall Recurrence
The goal of this clinical trial is to assess the safety and efficacy of combined ruxolitinib and neratinib in patients with chemotherapy-pretreated metastatic triple negative breast cancer. This trial will evaluate one dosing schedule of neratinib in ruxolitinib in patients with metTNBC with locoregional recurrence.
• A patient will be considered for enrollment in this study if all the following criteria are met:
‣ Female patients ≥18 years of age
⁃ Have a diagnosis of metastatic TNBC previously treated with standard anthracycline, cyclophosphamide, and taxane chemotherapy, unless there was a contraindication to doxorubicin, in which case prior treatment with this agent is not required.
‣ Note. TNBC defined as ER-negative tumors with ≤10% tumor nuclei immunoreactivity, or ER Low Positive as defined by the updated ASCO/CAP guidelines 2020.
⁃ Have not received more than 4 prior chemotherapy regimens for metastatic disease. Prior platinum and/or taxane therapy in the adjuvant or metastatic setting is permitted. Patients with more than 4 prior regimens may be allowed on study per physician discretion, if ECOG PS is 0-1.
⁃ Have locoregional (e.g., breast, chest wall, regional lymphatic) or pulmonary or hepatic metastatic disease that is amenable to core needle biopsy. If a research biopsy from a patient's metastatic disease cannot be safely obtained, a skin biopsy is permitted. If a skin biopsy cannot be safely obtained, patients may still be eligible, per physician discretion.
⁃ Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
⁃ Have adequate hematologic function, defined by:
• Absolute neutrophil count (ANC) \>1500/µL
∙ Platelet count ≥100,000/ µL
∙ Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
⁃ Have adequate liver function, defined by:
• AST and ALT ≤2.5 x the upper limit of normal (ULN) or ≤5 x ULN in presence of liver metastases
∙ Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels \>1.5 × ULN
⁃ Have adequate renal function, defined by:
‣ a. Serum creatinine ≤1.5 x ULN or calculated creatinine clearance of ≥30 mL/min
⁃ Patients who have a history of brain metastasis are eligible for the study provided that all the following criteria are met:
‣ Brain metastases which have been treated
‣ Off-treatment with steroids before administration of the first dose of treatment
‣ No ongoing requirement for dexamethasone or anti-epileptic drugs
‣ No clinical or radiological evidence of progression of brain metastases
‣ Patients must be accessible for treatment and follow-up.
‣ All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry.