OGX-011 and Docetaxel in Treating Women With Locally Advanced or Metastatic Breast Cancer

A Phase II Study of a Second Generation Clusterin Antisense Oligonucleotide (OGX-011) in Combination With Docetaxel in Advanced Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. OGX-011 may help docetaxel kill more tumor cells by making tumor cells more sensitive to the drug.

PURPOSE: This phase II trial is studying how well giving OGX-011 together with docetaxel works in treating women with locally advanced or metastatic breast cancer.

OBJECTIVES:

Primary

• Determine the efficacy of OGX-011 and docetaxel, in terms of objective tumor response rate, in women with locally advanced or metastatic breast cancer.

Secondary

• Determine the tolerability and toxicity of this regimen in these patients.
• Determine the time to progression and overall survival of patients treated with this regimen.

OUTLINE: This is an open-label, nonrandomized, multicenter study.

Patients receive OGX-011 IV over 2 hours on days -7, -5, -3, 1, 8, and 15 of course 1 and on days 1, 8, and 15 of all subsequent courses. Patients also receive docetaxel IV over 1 hour on days 1 and 8 of all courses. Treatment repeats every 21 days* for up to 10 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Course 1 is 28 days in length and all subsequent courses (courses 2-10) are 21 days in length.

After completion of study treatment, patients are followed at 4 weeks and then periodically until disease progression.

PROJECTED ACCRUAL: Approximately 42 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

  • Metastatic or locally advanced disease
  • Not curable with standard therapy

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

  • Lesion must be outside of the previously irradiated field

    • If the sole site of disease is in a previously irradiated field, there must be evidence of disease progression or new lesions in the irradiated field

• No known CNS metastases

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Platelet count ≥ 100,000/mm^3
• Absolute granulocyte count ≥ 1,500/mm^3
• PTT, PT, and INR normal
• No known bleeding disorder

Hepatic

• Bilirubin normal
• AST and ALT ≤ 1.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No significant cardiac dysfunction

Immunologic

• No active uncontrolled infection
• No history of serious allergic reaction to taxanes, including paclitaxel or docetaxel

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No preexisting neuropathy ≥ grade 2
• No other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
• No other serious medical condition or illness that would preclude study participation
• No significant neurological disorder that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior trastuzumab (Herceptin^®) allowed

Chemotherapy

• Recovered from prior chemotherapy

• At least 6 months since prior adjuvant chemotherapy (taxanes allowed)

• At least 4 weeks since prior chemotherapy for advanced disease

  • No prior taxanes for advanced disease

• No more than 1 prior chemotherapy regimen for advanced disease

• No other concurrent chemotherapy

Endocrine therapy

• At least 1 week since prior hormonal therapy

Radiotherapy

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy

  • Low-dose, nonmyelosuppressive radiotherapy allowed within 4 weeks before study entry at the discretion of the investigator

• No prior radiotherapy ≥ 30% of functioning bone marrow

• No concurrent radiotherapy

Surgery

• At least 3 weeks since prior major surgery and recovered (wound healing must have occurred)

Other

• More than 4 weeks since prior investigational agents or new anticancer therapy
• No concurrent therapeutic anticoagulation therapy except low-dose oral anticoagulant therapy (i.e., 1 mg of oral warfarin once a day) or low molecular weight heparin
• No other concurrent investigational therapy
• No other concurrent cytotoxic therapy