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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

Phase 1
18 Years
Not Enrolling
Carcinoma Breast Stage IV

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Trial Information

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

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.

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

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

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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility and maximum tolerated dose

Outcome Description:

Combination of Velcade and Herceptine in breast metastatic patients

Outcome Time Frame:

before recurrence

Safety Issue:


Principal Investigator

Fatima Cardoso, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Jules Bordet Institute


Belgium: Federal Agency for Medicines and Health Products, FAMHP

Study ID:

Herceptin-proteasome inhibitor



Start Date:

October 2003

Completion Date:

December 2007

Related Keywords:

  • Carcinoma Breast Stage IV
  • HER-2 positive
  • metastatic breast cancer patients
  • Breast Neoplasms
  • Carcinoma