PS-341 in Treating Women With Metastatic Breast Cancer

Phase II Trial Of PS-341 In Metastatic Breast Cancer

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

Study Overview

• Status: Completed
• Conditions: Stage IV Breast Cancer; Recurrent Breast Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: bortezomib

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Other: laboratory biomarker analysis; Correlative studies; Drug: bortezomib; Given IV; Other Names: MLN341; LDP 341; VELCADE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression	Will be reported using the Kaplan-Meier method with 95% confidence intervals indicated.	Up to 3 years
Overall survival	Will be reported using the Kaplan-Meier method with 95% confidence intervals indicated.	Up to 3 years
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
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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Massimo Cristofanilli, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start: August 1, 2001
• Primary Completion (Actual): August 1, 2004

Study Registration Dates

• First Submitted: October 11, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): January 23, 2013
• Last Update Submitted That Met QC Criteria: January 22, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: NCI-2012-02422; N01CM17003 (U.S. NIH Grant/Contract); ID00-308; CDR0000068976 (Registry Identifier: PDQ (Physician Data Query))