A Study of Tetrathiomolybdate (TM) Plus Capecitabine

Launched by DARTMOUTH-HITCHCOCK MEDICAL CENTER · Nov 15, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating the effects of a new treatment combination for patients with high-risk triple negative breast cancer, which is a type of cancer that does not respond to some common treatments. The study is looking at whether adding a drug called tetrathiomolybdate (TM) to the standard treatment of capecitabine and pembrolizumab can improve outcomes for patients who have already undergone initial chemotherapy and surgery but still have residual disease. The trial has two parts: the first part will assess the safety of this combination, while the second part will compare the effectiveness of the combination treatment against capecitabine alone.

To be eligible for this trial, participants must be adults aged 18 or older with confirmed triple negative breast cancer that has not spread to other parts of the body. They should have completed at least six cycles of standard chemotherapy and had surgery, but still have some cancer remaining. Participants will need to meet certain health criteria and agree to use birth control during the study to avoid potential risks to a developing fetus. If you join this trial, you can expect close monitoring and care from the research team as they evaluate the safety and effectiveness of the new treatment approach.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Patients must have histologically confirmed breast malignancy that is Triple negative tumors as defined as ER and PR \<1% and HER2 negative as per ASCO/CAP guidelines
• • 2. The patient must have completed standard neoadjuvant chemotherapy which constitutes at least 6 cycles of chemotherapy.
• • 3. Phase Ib: Patients must have residual invasive carcinoma, at minimum in one of the following capacities: (1) node positive disease after treatment without residual invasive carcinoma in the breast; (2) RCB 2 or RCB 3 MDAH Calculator; Standard therapy consists of the following: (1) Local therapy: (a) Lumpectomy or mastectomy to negative margins. (b) Sentinel lymph node biopsy or axillary node dissection; (c) Radiation therapy to breast if patient received a lumpectomy and per investigator choice if considering chest wall/extended field RT. (2) 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). Patients 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: Patients must have residual invasive carcinoma, at minimum in one of the following capacities: (1) node positive disease after treatment without residual invasive carcinoma in the breast; (2) RCB 2 or RCB 3 MDAH Calculator; Standard therapy consists of the following: (1) Local therapy: (a) Lumpectomy or mastectomy to negative margins. (b) Sentinel lymph node biopsy or axillary node dissection; (c) Radiation therapy to breast if patient received a lumpectomy and per investigator choice if considering chest wall/extended field RT. (2) 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. Patients will be stratified by: (1) Treatment (chemotherapy vs chemotherapy + immunotherapy); (2) Age (Age ≤ 40 yrs vs \> 40 yrs); and (3) RCB 2 vs RCB 3. These important stratification factors represent variables that are known to affect outcome for patients with TNBC.
• • 4. At least two weeks must have elapsed from last chemotherapy or radiation therapy. At least 4 weeks must have elapsed from most recent surgery.
• • 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. Previous treatment with capecitabine is not allowed.
• • 7. 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.
• • 8. KPS 90 or 100.
• • 9. Life expectancy of greater than 3 months.
• 10. Patients must have normal organ and marrow function as defined below:
• • hemoglobin \>10mg/dL
• • absolute neutrophil count \>1,500/ µL
• • platelets \>100,000/µL
• • total bilirubin \<1.5 x normal institutional limits
• • AST (SGOT)/ALT (SGPT) \<1.5 X institutional upper limit of normal
• • 11. Antiresorptive therapy and denosumab may be administered.
• • 12. Patients must be on stable medical therapy for at least 2 weeks if they are being treated medically for their chemotherapy induced peripheral neuropathy.
• • 13. The effects of TM on the developing human fetus are unknown. For this reason, women of childbearing 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.
• • 14. Ability to understand and the willingness to sign a written informed consent document.
• • 15. Normal B12 levels.
• Exclusion Criteria:
• • 1. Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study. Patients who have had surgery within 4 weeks.
• • 2. Patients who have received capecitabine or who are on warfarin
• • 3. Patients who had their final breast surgery more than 12 weeks prior to study start.
• • 4. Phase Ib: patients who have not received neoadjuvant immunotherapy and/or do not plan to continue treatment with immunotherapy for at least the first cycle of study treatment.
• • 5. Objective evidence of breast cancer.
• • 6. Metastatic disease
• • 7. Carcinomatous meningitis or active parenchymal brain metastases.
• • 8. Estimated creatinine clearance \< 60 ml/min
• • 9. History of allergic reactions attributed to compounds of similar chemical or biologic composition to TM or capecitabine.
• • 10. 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.
• • 11. 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.