Phase II Study of Tetrathiomolybdate (TM) in Patients With Breast Cancer
Phase II Study of Tetrathiomolybdate (TM) in Patients With Breast Cancer
Patients with moderate to high risk primary breast cancer (Stage II with more than 4 lymph
 nodes involved with cancer) III or Stage IV (without evidence of disease) will take
 tetrathiomolybdate (TM) pills for two years.

 The objectives of the study are to:

 -  Assess the safety and tolerability of tetrathiomolybdate in patients with breast cancer
 at high risk of tumor recurrence.

 -  Observe the disease-free survival of patients in this trial.

 -  Conduct background scientific experiments on tumor tissue and blood of patients in this
 study
Patients with moderate to high risk primary breast cancer -Stage III, Triple negative (T= 4
 cm N0, any N+), Stage IV (without evidence of disease) will take tetrathiomolydbate (TM)
 pills for two years.

 Extension study 1 - If patients are shown to be copper depleted, they are given the option to
 continue to receive TM for an additional 2 years.

 Extension study 2 - Open to patients who are stage 4 NED, 10 involved lymph nodes or triple
 negative molecular subtype and candidates will continue for months 49-72.

 Extension study 3 - Open to patients who are stage 4 NED receiving a benefit from TM. These
 subjects can continue receiving TM for 73-96 months.

 Extension study 4 - Open to patients who are stage 4 NED receiving a benefit from TM. These
 subject can continue receiving TM for 97-120 months.
Inclusion Criteria:

 1. Patients must have histologically confirmed breast malignancy that is:

 -  High risk stage II breast cancer (≥4 positive lymph nodes),

 -  Stage III breast cancer, including inflammatory breast cancer

 -  Stage IV breast cancer in a complete remission (bone only not allowed unless the
 bone scan is normal).

 2. The patient must have had what is considered standard adjuvant systemic therapy that
 may include chemotherapy, hormonal therapy and radiation therapy. They may have
 undergone high dose chemotherapy with stem cell support as part of their therapy in
 the adjuvant or metastatic setting. The patient is allowed to continue to take
 adjuvant hormonal therapy (for high risk adjuvant patients) and may be allowed to be
 on hormonal consolidation post transplant if they are without evidence of disease
 after a transplant for metastatic breast cancer. The patient cannot be actively
 receiving chemotherapy or any biologic agent to treat their breast cancer.

 3. Six weeks must elapse from last chemotherapy or radiation therapy.

 4. The patient must have had definitive surgical therapy for their breast cancer. This
 includes lumpectomy and axillary dissection or mastectomy.

 5. No 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)

 6. 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.

 7. ECOG performance status < 1

 8. Life expectancy of greater than 3 months.

 9. Patients must have normal organ and marrow function as defined below:

 -  hemoglobin >10mg/dL

 -  absolute neutrophil count >1,500/mL

 -  platelets >100,000/mL

 -  total bilirubin < 1.5 x normal institutional limits

 -  AST(SGOT)/ALT(SGPT) <1.5 X institutional upper limit of normal

 10. Erythropoietin alpha is allowed, as indicated.

 11. Bisphosphonates may be administered if they were started prior to starting this
 therapy.

 12. Patients must be on stable medical therapy for at least 2 weeks if they are being
 treated medically for their peripheral neuropathy.

 13. Concurrent herceptin is not allowed.

 14. The effects of TM on the developing human fetus are unknown. For this reason, women of
 child-bearing potential and men must agree to use adequate contraception (hormonal or
 barrier method of birth control; abstinence) prior to study entry and for the duration
 of study participation. Should a woman become pregnant or suspect she is pregnant
 while participating in this study, she should inform her treating physician
 immediately.

 15. Ability to understand and the willingness to sign a written informed consent document.

 Exclusion Criteria:

 1. Patients who have had chemotherapy or radiotherapy within 6 weeks prior to entering
 the study.

 2. Objective evidence of breast cancer.

 3. Carcinomatous meningitis or history of neoplastic parenchymal brain disease.

 4. Serum creatinine >1.5 x normal.

 5. History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to TM.

 6. Pregnant women 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.

 7. 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 with TM.