Phase II Study of Tetrathiomolybdate (TM) in Patients With Breast Cancer

NCT00195091 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 18-0230309006307
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Time to Progression for Patients With Breast Cancer Treated With Study Drug

  duration of study

Study Arms (1)

Tetrathiomolybdate (TM)

EXPERIMENTAL

Induction period - TM 40 mg is administered three x per day with meals and TM 60 mg at bedtime for a total of 4 doses (180 mg) per day. Maintenance Period - Total TM dose per day will be in 20 mg increments to tailor the therapy to individualized patient needs to maintain the Cp level at 5-17mg/dL. Thus all dose modifications will be dependent on individual patient Cp levels. TM 40 mg p.o. BID with meals and TM 20 mg at bedtime. Subjects who have no evidence of disease (NED) and are receiving a benefit of TM can continue taking the drug for up to 120 months.

Drug: Tetrathiomolybdate

Interventions

Tetrathiomolybdate DRUG

Induction with Tetrathiomolybdate (TM) Tetrathiomolybdate 40 mg. p.o. TID with meals and tetrathiomolybdate 60 mg at bedtime for a total of 4 doses (180 mg) per day. Induction goal Total tetrathiomolybdate dose per day = 180 mg until serum ceruloplasmin (Cp) level decreases to 5-15mg/dL. When target Cp window is reached, then the maintenance phase begins. Maintenance with Tetrathiomolybdate Total tetrathiomolybdate dose per day = 100 mg Tetrathiomolybdate 40 mg p.o. BID with meals and tetrathiomolybdate 20 mg at bedtime.

Also known as: TM

Tetrathiomolybdate (TM)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• Six weeks must elapse from last chemotherapy or radiation therapy.
• The patient must have had definitive surgical therapy for their breast cancer. This includes lumpectomy and axillary dissection or mastectomy.
• 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)
• 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.
• ECOG performance status \< 1
• Life expectancy of greater than 3 months.
• Patients must have normal organ and marrow function as defined below:
• hemoglobin \>10mg/dL
• absolute neutrophil count \>1,500/mL
• platelets \>100,000/mL

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 6 weeks prior to entering the study.
• Objective evidence of breast cancer.
• Carcinomatous meningitis or history of neoplastic parenchymal brain disease.
• Serum creatinine \>1.5 x normal.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TM.
• 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.
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Weill Medical College of Cornell University: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Related Publications (1)

• Ramchandani D, Berisa M, Tavarez DA, Li Z, Miele M, Bai Y, Lee SB, Ban Y, Dephoure N, Hendrickson RC, Cloonan SM, Gao D, Cross JR, Vahdat LT, Mittal V. Copper depletion modulates mitochondrial oxidative phosphorylation to impair triple negative breast cancer metastasis. Nat Commun. 2021 Dec 15;12(1):7311. doi: 10.1038/s41467-021-27559-z.

  PMID: 34911956 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Breast Neoplasms

Interventions

tetrathiomolybdate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Dr. Tiffany Traina MD
• Organization: Memorial Sloan Kettering Cancer Center

trainat@MSKCC.ORG

646-888-4558

Study Officials

• Linda Vahdat, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2005
• First Posted: September 19, 2005
• Study Start: December 1, 2003
• Primary Completion: March 2, 2023
• Study Completion: March 2, 2023
• Last Updated: May 16, 2025
• Results First Posted: April 23, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)