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

This study has been completed.
Sponsor:
Information provided by:
Jules Bordet Institute
ClinicalTrials.gov Identifier:
NCT00199212
First received: September 13, 2005
Last updated: February 23, 2011
Last verified: February 2011
  Purpose

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 Intervention Phase
Carcinoma Breast Stage IV
Drug: Combination of trastuzumab and PS-341
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Jules Bordet Institute:

Primary Outcome Measures:
  • Feasibility and maximum tolerated dose [ Time Frame: before recurrence ] [ Designated as safety issue: Yes ]
    Combination of Velcade and Herceptine in breast metastatic patients

  • Time of recurrence [ Time Frame: time of recurrence ] [ Designated as safety issue: Yes ]
    safety and tolerability of combinaison before recurrence of metastatic breast cance


Secondary Outcome Measures:
  • Response rate [ Time Frame: time before response rate ] [ Designated as safety issue: Yes ]
    Tolerability and safety of combination of velcade and Herceptine


Enrollment: 19
Study Start Date: October 2003
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Combination of trastuzumab and PS-341
    Trastuzumab and velcade are used according standard procedure
    Other Names:
    • PS-341, velcade
    • trastuzumab, herceptine
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00199212

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

No publications provided

Responsible Party: Dr Fatima Cardoso, Institut Jules Bordet
ClinicalTrials.gov Identifier: NCT00199212     History of Changes
Other Study ID Numbers: Herceptin-proteasome inhibitor
Study First Received: September 13, 2005
Last Updated: February 23, 2011
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

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

Additional relevant MeSH terms:
Breast Neoplasms
Carcinoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Trastuzumab
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014