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
Overview
- Phase
- Early Phase 1
- Intervention
- Neratinib Oral Tablet
- Conditions
- Metastatic Triple-Negative Breast Carcinoma
- Sponsor
- Baylor Research Institute
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Objective Response Rate
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
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.
Detailed Description
Metastatic triple negative breast cancer (metTNBC) lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), making it unresponsive to both endocrine and HER2-targeted therapies. Chest wall recurrence is common in patients with treatment resistant metTNBC and leads to substantial morbidity as no successful therapeutic options exist. Patients suffer with escalated progression of disease across the entire chest wall with substantial wound control issues. Chest wall recurrence generally occurs within one year following chemotherapy or immunotherapy given with curative intent, and in general signifies metTNBC that is primary resistant to standard therapy. There is long standing evidence that EGFR is an important signaling pathway in metTNBC as this cancer overexpresses EGFR compared to other breast cancer subtypes. This exposes a pathway that is targetable for treatment, making EGFR a compelling molecular therapeutic target in metTNBC. Another key contributor to progression of TNBC is the JAK/STAT3 signaling pathway and assessments of EGFR have shown that it is a positive regulator of STAT3 that drives proliferation and survival of metTNBC. The investigators hypothesize that combined inhibition of EGFR and JAK/STAT3 using neratinib and ruxolitinib will lead to greater inhibition of the critically important EGFR pathway in TNBC with greater efficacy than targeting EGFR or JAK/STAT3 alone.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •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-
- •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
Exclusion Criteria
- •A patient will be ineligible for inclusion in this study any of the following criteria are met:
- •Has received a live vaccine or live-attenuated vaccine within 30 days of the first dose of study treatment. Administration of killed vaccines is allowed.
- •Has peripheral neuropathy ≥grade 2
- •Has completed previous radiotherapy for metastatic disease \<2 weeks prior to study treatment initiation
- •Has an active infection requiring systemic therapy
- •Has significant cardiovascular disease, such as:
- •History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass grafting within the last 6 months
- •Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV, or history of CHF NYHA class III or IV.
- •Has a known history of active tuberculosis
- •Women who are pregnant or lactating. All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug.
Arms & Interventions
neratinib + ruxolitinib
There is only one arm
Intervention: Neratinib Oral Tablet
neratinib + ruxolitinib
There is only one arm
Intervention: Ruxolitinib Oral Tablet
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: 18 months
Calculate objective response rate (CR+PR) associated with neratinib in combination ruxolitinib. Objective response rate will be calculated by defining the proportion of patients who have a complete or partial response to the study therapy, as determined by the treating physician.
Secondary Outcomes
- Duration of Response(18 months)