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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 : April 20, 2021
Sponsor:
Collaborator:
Weill Medical College of Cornell University
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE September 14, 2005
First Posted Date  ICMJE September 19, 2005
Last Update Posted Date April 20, 2021
Study Start Date  ICMJE December 2003
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2007)
time to progression for patients with breast cancer treated with study drug [ Time Frame: duration of study ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Study of Tetrathiomolybdate (TM) in Patients With Breast Cancer
Official Title  ICMJE A Phase II Study of Tetrathiomolybdate (TM) in Patients With Breast Cancer at Moderate to High Risk of Recurrence
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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE 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
Study Arms  ICMJE 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.

Intervention: Drug: Tetrathiomolybdate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: December 11, 2007)
50
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00195091
Other Study ID Numbers  ICMJE 18-023
0309006307 ( Other Identifier: Weill Cornell Medical College )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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.
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Weill Medical College of Cornell University
Investigators  ICMJE
Principal Investigator: Linda Vahdat, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP