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PS-341 in Treating Women With Metastatic Breast Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00025584
First received: October 11, 2001
Last updated: January 22, 2013
Last verified: January 2013
History of Changes
  Purpose

PS-341 may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Phase II trial to study the effectiveness of PS-341 in treating women who have metastatic breast cancer


Condition Intervention Phase
Recurrent Breast Cancer
Stage IV Breast Cancer
 Drug: bortezomib
Other: laboratory biomarker analysis
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial Of PS-341 In Metastatic Breast Cancer

Resource links provided by NLM:

Drug Information available for: Bortezomib
U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective tumor response (CR + PR) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    The agent would be of definite interest for further investigation if the associated response rate is at least 30% (p1), and would not be of further interest if the response rate is below 10% (p0).


Secondary Outcome Measures:
  • Time to progression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will be reported using the Kaplan-Meier method with 95% confidence intervals indicated.

  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will be reported using the Kaplan-Meier method with 95% confidence intervals indicated.

  • Correlation between variations in the serum levels of adhesion molecules and angiogenic factors [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Will be evaluated and descriptive analysis will be performed.

  • Tissue markers of biological activity [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    Will be described in case of lesions amenable to tissue biopsy. The plasma pharmacodynamics of PS-341 as measured by the 20S-proteosome assay, will be used to measured the biological activity of the drug and correlated with response to treatment and variations in biomarkers.


Enrollment: 35
Study Start Date: August 2001
Primary Completion Date: August 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib)
Patients receive PS-341 IV over 3-5 seconds twice weekly on weeks 1 and 2. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
 Drug: bortezomib
Given IV
Other Names:
  • LDP 341
  • MLN341
  • VELCADE
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the efficacy of PS-341, in terms of response rate, in women with metastatic breast cancer.

SECONDARY OBJECTIVES:

I. Determine the clinical activity of this drug, in terms of progression-free survival, in these women.

II. Determine the toxicity profile and tolerability of this drug in these women.

III. Determine the pharmacodynamics of this drug in these women.

OUTLINE:

Patients receive PS-341 IV over 3-5 seconds twice weekly on weeks 1 and 2. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A maximum of 12-35 patients will be accrued for this study within 9-12 months.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed invasive breast cancer

    • Clinical and/or radiological evidence of stage IV disease
  • Relapsed or resistant disease within 6-12 months after completion of prior chemotherapy with doxorubicin or epirubicin and/or paclitaxel or docetaxel foradvanced disease or in the adjuvant setting

  • At least 1 unidimensionally measurable lesion

    • At least 20 mm by conventional techniques
    • At least 10 mm by spiral CT scan
    • No bone metastases as only measurable site
    • Pleural or peritoneal effusions not acceptable as measurable disease
  • No known brain metastases

  • Hormone receptor status:

    • Estrogen receptor-negative
    • Estrogen receptor-positive
  • Female
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 60-100%
  • More than 12 weeks
  • WBC at least 3,000/mm^3
  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin normal
  • AST or ALT no greater than 2.5 times upper limit of normal
  • Creatinine normal
  • Creatinine clearance at least 60 mL/min
  • No acute ischemia or significant conduction abnormality by EKG
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • LVEF greater than 50%
  • No uncontrolled concurrent illness
  • No psychiatric illness or social situation that would preclude study
  • No ongoing or active infection
  • No prior allergic reaction(s) to compounds of similar chemical or biologic composition to PS-341
  • No other malignancy within the past 5 years except carcinoma in situ of the cervix or basal cell skin cancer
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier-method contraception
  • See Chemotherapy
  • See Disease Characteristics

  • No more than 1 prior chemotherapy regimen for metastatic disease

    • High-dose regimen or bone marrow transplantation considered 1 prior regimen
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • Prior hormonal therapy for metastatic disease or in adjuvant setting allowed
  • Prior localized radiotherapy allowed if it does not influence the signal evaluable lesion
  • At least 4 weeks since prior radiotherapy and recovered
  • At least 2 weeks since prior minor surgery and recovered
  • At least 4 weeks since prior major surgery and recovered
  • No other concurrent investigational agent
  • No other concurrent investigational or commercial agents or therapies to treat this malignancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00025584

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Massimo Cristofanilli M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00025584     History of Changes
Other Study ID Numbers: NCI-2012-02422, ID00-308, N01CM17003, CDR0000068976
Study First Received: October 11, 2001
Last Updated: January 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Bortezomib
 Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013