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PS-341 in Combination With Herceptin in Advanced Breast Cancer That Overexpresses HER-2

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. Identifier: NCT00199212
Recruitment Status : Completed
First Posted : September 20, 2005
Last Update Posted : February 24, 2011
Information provided by:
Jules Bordet Institute

Brief Summary:
The main objective of this study is to determine the feasibility of the combination of the proteasome inhibitor bortezomib (PS-341, Velcade) with trastuzumab (Herceptin) and to determine the best dose of bortezomib to combine with two trastuzumab schedules, weekly and 3-weekly.

Condition or disease Intervention/treatment Phase
Carcinoma Breast Stage IV Drug: Combination of trastuzumab and PS-341 Phase 1

Detailed Description:

Phase 1 study to determine the feasibility of the combination of the proteasome inhibitor bortezomib (PS-341, Velcade) with trastuzumab (Herceptin) given either weekly or 3-weekly.

Additionally, hints about efficacy of the combination will be looked upon.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open Label, Dose-escalating Study of the Proteasome Inhibitor PS-341 in Combination With Two Schedules of Herceptin, in Patients With Advanced Breast Cancer That Overexpresses HER-2
Study Start Date : October 2003
Primary Completion Date : December 2007
Study Completion Date : December 2007

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Intervention Details:
    Drug: Combination of trastuzumab and PS-341
    Trastuzumab and velcade are used according standard procedure
    Other Names:
    • PS-341, velcade
    • trastuzumab, herceptine

Primary Outcome Measures :
  1. Feasibility and maximum tolerated dose [ Time Frame: before recurrence ]
    Combination of Velcade and Herceptine in breast metastatic patients

  2. Time of recurrence [ Time Frame: time of recurrence ]
    safety and tolerability of combinaison before recurrence of metastatic breast cance

Secondary Outcome Measures :
  1. Response rate [ Time Frame: time before response rate ]
    Tolerability and safety of combination of velcade and Herceptine

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Female gender
  2. Age >= 18 years
  3. ECOG performance status < 2
  4. Histologically proven diagnosis of breast cancer
  5. Locally advanced and/or metastatic disease
  6. Life expectancy of three months or longer
  7. No concurrent second malignancy (except for adequately treated basal cell carcinoma of the skin, in situ carcinoma of the cervix or contralateral breast cancer). Any prior second malignancy must be in remission for >= 5 years (except for contralateral breast cancer).
  8. No other serious illness or medical condition including:

    • History of documented congestive heart failure; angina pectoris requiring antianginal medication; evidence of recent (< 6 months) transmural infarction on electrocardiogram (ECG); poorly controlled hypertension (e.g. systolic > 180 mmHg or diastolic greater than 100 mmHg); clinically significant valvular heart disease; or high-risk uncontrolled arrhythmias.
    • Chronic lung disease
    • History of significant neurological or psychiatric disorders that would prohibit the understanding and giving of informed consent, including psychotic disorders, mental retardation, and dementia.
    • Active concurrent infection
  9. No symptomatic central nervous system (CNS) metastases
  10. No rapidly progressive visceral metastases requiring immediate chemotherapy
  11. No concurrent anti-cancer treatment is allowed.
  12. Prior investigational biological agents are allowed, with the exception of anti-HER-2 therapy for any reason.
  13. Previous hormonal therapy is allowed, as adjuvant and/or for metastatic breast cancer (MBC).
  14. Adjuvant and MBC chemotherapy allowed, provided that a minimum of 4 weeks interval has elapsed between last chemotherapy administration and first study drug dose. All patients who, in the opinion of the investigator, could benefit from single agent Herceptin® and are not considered suitable for treatment with chemotherapy plus Herceptin® can be considered for this protocol.
  15. A maximum cumulative dose of previous doxorubicin < 360 mg/m2 or a maximum cumulative dose of epirubicin < 720 mg/m2
  16. Concomitant use of bisphosphonates is allowed, however if bisphosphonates are started during the trial for worsening bone pain, patients should be assessed for possible progressive disease.
  17. Adequate organ function as defined by:

    • Neutrophils >= 1.5 x 10^9/L
    • Platelets >= 100 x 10^9/L
    • Bilirubin <= 1.5 x upper limit of normal (ULN)
    • Transaminases <= 2.5 x ULN or <= 5 x ULN if liver metastasis
    • Creatinine <= 1.5 x ULN
  18. Overexpression of HER-2 in the invasive component of the primary tumor, according to one of the following definitions:

    • 3+ overexpression by immunohistochemistry (IHC) or
    • 2+ overexpression by IHC and fluorescence in situ hybridization (FISH) test demonstrating c-erbB2 gene amplification (ratio of c-erbB2 gene signals to centromere 17 signals > 2)
  19. Baseline left ventricular ejection fraction (LVEF) > 50% measured by multiple gated acquisition scan (MUGA) or echocardiography
  20. Evaluable or uni-dimensionally measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria
  21. Women of childbearing potential must have a negative serum or urine pregnancy test and be willing to use acceptable methods of birth control.
  22. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
  23. Before patient registration/randomization, informed consent must be given according to International Conference of Harmonization/European Union Good Clinical Practice (ICH/EU GCP), and national/local regulations.

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 identifier (NCT number): NCT00199212

Jules Bordet Institute
Brussels, Belgium, 1000
Sponsors and Collaborators
Jules Bordet Institute
Principal Investigator: Fatima Cardoso, MD Jules Bordet Institute

Responsible Party: Dr Fatima Cardoso, Institut Jules Bordet Identifier: NCT00199212     History of Changes
Other Study ID Numbers: Herceptin-proteasome inhibitor
First Posted: September 20, 2005    Key Record Dates
Last Update Posted: February 24, 2011
Last Verified: February 2011

Keywords provided by Jules Bordet Institute:
HER-2 positive
metastatic breast cancer patients

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Proteasome Inhibitors
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action