PS-341 in Treating Women With Metastatic Breast Cancer

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Recurrent Breast Cancer; Stage IV Breast Cancer

Treatments: Other: laboratory biomarker analysis; Drug: bortezomib

Study type: Interventional

Funder types: NIH

Identifiers

NCT00025584

N01CM17003 (U.S. NIH Grant/Contract)

ID00-308

CDR0000068976 (Registry Identifier)

NCI-2012-02422

Details and patient eligibility

About

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

Full 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.

Enrollment: 35 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

Treatment (bortezomib)

Experimental group

Description:

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.

Treatment:

Other: laboratory biomarker analysis

Drug: bortezomib