A Pilot Study of the Combination of Entinostat With Capecitabine in High Risk Breast Cancer After Neo-adjuvant Therapy
Overview
- Phase
- Phase 1
- Intervention
- Entinostat
- Conditions
- Metastatic Breast Cancer
- Sponsor
- University of Virginia
- Enrollment
- 13
- Locations
- 2
- Primary Endpoint
- Frequency of adverse events (AEs) in participants with high-risk breast cancer after neo-adjuvant therapy
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to learn about the safety and side effects of combining entinostat, an investigational drug, with capecitabine, a drug commonly used in breast cancer (BC), in both participants with metastatic breast cancer (MBC) and then participants with high-risk breast cancer after neo-adjuvant therapy.
Detailed Description
In order to identify the maximum dose that should be used in future participants, the first participants will start at a low dose of both drugs. If the participants on this dose level tolerate the treatment well without too many side effects, the next participants will receive a higher dose of one of the medications, and if those participants also tolerate the treatment well, then the drugs will continue to be increased with the next participants until a maximum dose that participants tolerate well is reached. Participants in both groups will receive entinostat on days 1, 8, and 15 of each 21-day cycle and capecitabine on days 1-14 of each cycle. MBC participants may receive this treatment as long as they do not have disease progression or side effects that require them to stop study treatment while participants with high-risk BC after neo-adjuvant therapy will receive up to 8 cycles of study treatment as long as they do not have disease progression or side effects that require them to stop study treatment. While participants are on study treatment, they will have regular physical exams and labs. After participants finish study treatment, they should be followed by their primary oncologist at least once a year. Study staff will also be in contact by phone at least once a year for 10 years.
Investigators
Patrick Dillon, MD
Principal Investigator
University of Virginia
Eligibility Criteria
Inclusion Criteria
- •Disease Characteristics by Dose Escalation Phase and Expansion Phase:
- •Part A: Dose Escalation Phase:
- •Patients must have a histologically confirmed diagnosis of stage IV invasive breast cancer.
- •Patients can have breast cancer with positive OR negative estrogen and progesterone receptor status. Patients must have negative HER-2 receptor status. Estrogen, progesterone, and HER2 receptor status must be assessed according to ASCO/CAP guidelines. ER or PR positivity is defined as ≥ 1% positive nuclear staining. HER-2 is negative if tumor testing shows: a) IHC negative (0 or 1+) or b) ISH negative using single probe or dual probe. If HER-2 IHC is 2+, ISH must be performed and negative. HER-2 equivocal is not eligible.
- •Part B: Expansion Phase:
- •Patients must have a histologically confirmed diagnosis of stage I-III invasive breast cancer.
- •Patients with multifocal, multicentric, synchronous bilateral and primary inflammatory breast cancers are allowed.
- •Multifocal disease is defined as more than one invasive cancer \< 2 cm from the largest lesion within the same breast quadrant.
- •Multicentric disease is defined as more than one invasive cancer ≥ 2 cm from the largest lesion within the same breast quadrant or more than one lesion in different quadrants.
- •Synchronous bilateral disease is defined as invasive breast cancer with positive lymph nodes (axillary or intramammary) in at least one breast, diagnosed within 30 days of each other. NOTE: The tumor with the highest recurrence score should be used.
Exclusion Criteria
- Not provided
Arms & Interventions
Entinostat and Capecitabine
Dose escalation of the combination of entinostat and capecitabine in MBC patients. This dose will be given to MBC patients and to BC patients with residual invasive disease after neoadjuvant chemotherapy and surgery. The dose combinations include: Combination 1: 3 mg/week entinostat, 800 mg/m2 twice a day for 14 days of capecitabine Combination 2: 5 mg/week entinostat, 800 mg/m2 twice a day for 14 days of capecitabine Combination 3: 3 mg/week entinostat, 1000 mg/m2 twice a day for 14 days of capecitabine Combination 4: 5 mg/week entinostat, 1000 mg/m2 twice a day for 14 days of capecitabine If a participant experiences unacceptable side effects, he or she will receive the next lowest dose combination. If he or she is on Combination 1, he or she will stop study treatment.
Intervention: Entinostat
Entinostat and Capecitabine
Dose escalation of the combination of entinostat and capecitabine in MBC patients. This dose will be given to MBC patients and to BC patients with residual invasive disease after neoadjuvant chemotherapy and surgery. The dose combinations include: Combination 1: 3 mg/week entinostat, 800 mg/m2 twice a day for 14 days of capecitabine Combination 2: 5 mg/week entinostat, 800 mg/m2 twice a day for 14 days of capecitabine Combination 3: 3 mg/week entinostat, 1000 mg/m2 twice a day for 14 days of capecitabine Combination 4: 5 mg/week entinostat, 1000 mg/m2 twice a day for 14 days of capecitabine If a participant experiences unacceptable side effects, he or she will receive the next lowest dose combination. If he or she is on Combination 1, he or she will stop study treatment.
Intervention: Capecitabine
Outcomes
Primary Outcomes
Frequency of adverse events (AEs) in participants with high-risk breast cancer after neo-adjuvant therapy
Time Frame: AEs from consent through 30 days following stopping study treatment. Study treatment-related serious adverse events (SAEs) anytime
Frequency of adverse events (AEs) in participants with high-risk BC after neo-adjuvant therapy at the determined MTDC.
Identification of a maximum tolerated dose combination (MTDC) of entinostat and capecitabine
Time Frame: During the first cycle of treatment (each cycle is 21 days) for each participant
This will be defined based on the number of "dose limiting toxicities" in participants at each dose level.
Severity (as graded with the Common Terminology Criteria for Adverse Events (CTCAE)) of adverse events (AEs) in participants with high-risk breast cancer after neo-adjuvant therapy
Time Frame: AEs from consent through 30 days following stopping study treatment. Study treatment-related serious adverse events (SAEs) anytime
Severity of adverse events (AEs) in participants with high-risk BC after neo-adjuvant therapy at the determined MTDC.
Secondary Outcomes
- Frequency of adverse events (AEs) in MBC participants at the determined MTDC.(AEs from consent through 30 days following stopping study treatment. Study treatment-related serious adverse events (SAEs) anytime)
- Severity (as graded with the CTCAE) of adverse events (AEs) in participants on both arms of the study at the determined MTDC(DLTs will be identified during the 1st cycle (each cycle is 21 days) of study treatment. AEs from consent through 30 days following completion of treatment. Study treatment-related SAEs will be collected starting at consent through end of study)
- Disease-free survival (DFS)(Participants will be followed for up to 10 years following completion of study therapy)
- Severity (as graded with the Common Terminology Criteria for Adverse Events (CTCAE)) of adverse events (AEs) in MBC participants(AEs from consent through 30 days following stopping study treatment. Study treatment-related serious adverse events (SAEs) will be collected starting at consent and continuing for the life of the study.)
- Frequency of adverse events (AEs) and dose-limiting toxicities (DLTs) in participants on both arms of the study at the determined MTDC.(DLTs will be identified during the 1st cycle (each cycle is 21 days) of study treatment. AEs from consent through 30 days following completion of treatment. Study treatment-related SAEs will be collected starting at consent through end of study)