PS-341 in Treating Women With Metastatic Breast Cancer

Stage IV Breast Cancer Clinical Trial

Official title:

Phase II Trial Of PS-341 In Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00025584
• Other study ID #: NCI-2012-02422
• Secondary ID: ID00-308N01CM170
• Status: Completed
• Phase: Phase 2
• First received: October 11, 2001
• Last updated: January 22, 2013
• Start date: August 2001

Study information

• Verified date: January 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. primary completion date: August 2004
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Recurrent Breast Cancer
• Stage IV Breast Cancer

Intervention

Drug:
• bortezomib
Given IV

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective tumor response (CR + PR)	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).	Up to 24 months	No
Secondary	Time to progression	Will be reported using the Kaplan-Meier method with 95% confidence intervals indicated.	Up to 3 years	No
Secondary	Overall survival	Will be reported using the Kaplan-Meier method with 95% confidence intervals indicated.	Up to 3 years	No
Secondary	Correlation between variations in the serum levels of adhesion molecules and angiogenic factors	Will be evaluated and descriptive analysis will be performed.	Up to 24 months	No
Secondary	Tissue markers of biological activity	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.	Up to 24 months	No