Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00195091
Recruitment Status : Active, not recruiting
First Posted : September 19, 2005
Last Update Posted : March 1, 2019
Sponsor:
Collaborator:
Weill Medical College of Cornell University
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

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

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Tetrathiomolybdate Phase 2

Detailed Description:

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Tetrathiomolybdate (TM) in Patients With Breast Cancer at Moderate to High Risk of Recurrence
Study Start Date : December 2003
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Tetrathiomolybdate (TM)

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

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.

Other Name: TM




Primary Outcome Measures :
  1. time to progression for patients with breast cancer treated with study drug [ Time Frame: duration of study ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00195091


Locations
Layout table for location information
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Weill Medical College of Cornell University
Investigators
Layout table for investigator information
Principal Investigator: Linda Vahdat, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00195091     History of Changes
Other Study ID Numbers: 18-023
0309006307 ( Other Identifier: Weill Cornell Medical College )
First Posted: September 19, 2005    Key Record Dates
Last Update Posted: March 1, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Molybdenum
Tetrathiomolybdate
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Trace Elements
Micronutrients
Nutrients