Capecitabine with or without Tetrathiomolybdate and Pembrolizumab for the Treatment of Triple Negative Breast Cancer at High Risk for Relapse

Inclusion Criteria

• Participants must have histologically confirmed breast malignancy that is a triple negative tumor defined as estrogen receptor (ER) and progesterone receptor (PR) < 1% and HER2 negative as per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
• The patient must have completed standard neoadjuvant chemotherapy which constitutes at least 6 cycles of chemotherapy
• PHASE IB: Participants must have residual invasive carcinoma, at minimum in one of the following capacities: * Node positive disease after treatment without residual invasive carcinoma in the breast * RCB 2 or RCB 3 MD Anderson Health (MDAH) Calculator Standard therapy consists of the following: * Local therapy: ** Lumpectomy or mastectomy to negative margins ** Sentinel lymph node biopsy or axillary node dissection ** Radiation therapy to breast if patient received a lumpectomy and per investigator choice if considering chest wall/extended field radiation therapy (RT) * Systemic therapy: ** Prior chemotherapy is required for patients entered on the trial. Neoadjuvant treatment should consist of the following standard therapy: Anthracycline and taxane based therapy (i.e. adriamycin, cytoxan (AC)->taxol (T), AC->T carboplatin (carbo), Keynote 522 regimen) or a non-anthracycline based chemo and immunotherapy regimen (NeoPACT). Participants must have received neoadjuvant pembrolizumab for the phase Ib only and plan to continue it in the adjuvant setting for at least the first cycle of treatment
• RANDOMIZED PHASE 2: Participants must have residual invasive carcinoma, at minimum in one of the following capacities: * Node positive disease after treatment without residual invasive carcinoma in the breast * RCB 2 or RCB 3 MDAH Calculator * Standard therapy consists of the following: ** Local therapy: *** Lumpectomy or mastectomy to negative margins *** Sentinel lymph node biopsy or axillary node dissection *** Radiation therapy to breast if patient received a lumpectomy and per investigator choice if considering chest wall/extended field RT. ** Systemic therapy: Prior chemotherapy is required for patients entered on the trial. Neoadjuvant treatment should consist of the following standard therapy: Anthracycline and taxane-based therapy (i.e. AC->T, AC->Tcarbo, Keynote 522 regimen) or a non-anthracycline based chemo and immunotherapy regimen (NeoPACT). Pembrolizumab is allowed. Participants will be stratified by: * Treatment (chemotherapy vs chemotherapy + immunotherapy) * Age (Age ≤ 40 yrs vs > 40 yrs); and * RCB 2 vs RCB 3 These important stratification factors represent variables that are known to affect outcome for patients with triple negative breast cancer (TNBC).
• At least two weeks must have elapsed from last chemotherapy or radiation therapy. At least 4 weeks must have elapsed from most recent surgery
• Karnofsky performance status (KPS) 90 or 100
• Life expectancy of greater than 3 months
• Hemoglobin ≥ 10mg/dL
• Absolute neutrophil count ≥ 1,500/ µL
• Platelets ≥ 100,000/µL
• Total bilirubin ≤ 1.5 x normal institutional limits
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 1.5 X institutional upper limit of normal
• Estimated creatinine clearance ≥ 60 ml/min
• Antiresorptive therapy and denosumab may be administered
• Participants must be on stable medical therapy for at least 2 weeks if they are being treated medically for their chemotherapy induced peripheral neuropathy
• The effects of TM on the developing human fetus are unknown. For this reason, females of childbearing potential and males must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence of vaginal intercourse if the participant or their partner is of childbearing potential) prior to study entry, for the duration of study treatment and one month after the end of study treatment. Participants must also agree to not donate sperm or ova prior to study entry and for the duration of study treatment and one month after the end of study treatment. Should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Normal B12 levels

Exclusion Criteria

• Participants who have received capecitabine or who are on warfarin, copper containing vitamins or supplements, or prophylactic colony-stimulating factors (i.e., granulocyte colony-stimulating factor [GCSF], etc.)
• Participants with clinical or radiologic evidence of disease after surgery and/or systemic treatment (by CT scan of chest, abdomen and pelvis and bone scan or PET scan prior to enrollment),including metastatic disease, carcinomatous meningitis or active parenchymal brain metastases
• Participants who had their final breast surgery more than 18 weeks prior to study start
• Participants with known BRCA mutations in whom treatment with adjuvant Olaparib is planned
• If a participant has already had dihydropyrimidine dehydrogenase (DYPD) testing and has a known mutation (however DYPD testing is not required for the trial)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TM or capecitabine
• Pregnant females are excluded from this study because TM has the potential to have teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TM, breastfeeding should be discontinued if the mother is treated with TM
• Because no dosing or adverse event data are currently available on the use of TM in patients <18 years of age, children are excluded from this study
• Participants who are receiving protease inhibitors. Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow suppressive therapy, HIV-positive patients receiving combination anti- retroviral therapy are excluded from the study because of possible pharmacokinetic interactions of protease inhibitors with TM. Similarly, participants who are receiving protease inhibitors to treat hepatitis C are excluded from the study