RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using
anastrozole may fight breast cancer by blocking the use of estrogen by the tumor cells.
Lonafarnib may stop the growth of tumor cells by blocking some of the enzymes needed for
their growth. It is not yet known whether giving anastrozole with lonafarnib is more
effective than giving anastrozole with placebo in treating breast cancer.
PURPOSE: This randomized phase II trial is studying anastrazole given with lonafarnib to see
how this regimen works compared to anastrozole given with placebo in treating postmenopausal
women with stage IIIB, stage IIIC, or stage IV breast cancer.
- Compare progression-free survival of postmenopausal women with hormone
receptor-positive stage IIIB, IIIC, or IV breast cancer treated with anastrozole in
combination with lonafarnib vs placebo.
- Compare the objective response rate in patients treated with these regimens.
- Compare duration of response in patients treated with these regimens.
- Compare overall survival of patients treated with these regimens.
- Determine exposure to these regimens in these patients.
- Compare the safety of these regimens in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter
study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral anastrozole once daily and oral lonafarnib twice daily on
- Arm II: Patients receive oral anastrozole once daily and oral placebo twice daily on
In both arms courses repeat every 28 days in the absence of disease progression or
Patients are followed every 4 weeks until disease progression and then every 12 weeks
PROJECTED ACCRUAL: A maximum of 110 patients (55 per treatment arm) will be accrued for this
- Histologically confirmed breast cancer
- Stage IIIB, IIIC, or IV disease
- Measurable or evaluable disease
- Measurable disease defined as masses with clearly defined margins AND at least 1
diameter ≥ 20 mm by radiography OR ≥ 10 mm by spiral CT scan
- Evaluable disease defined as masses without clearly defined margins on
radiological images OR no diameter ≥ 20 mm
- Patients with bone only disease eligible if disease is evaluable
- No brain metastases
- Hormone receptor status:
- Estrogen receptor- and/or progesterone receptor-positive
- ECOG 0-1
- Not specified
- Neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10.0 g/dL
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and ALT ≤ 2 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- Creatinine ≤ 1.5 times ULN
- No significant QTcF prolongation (i.e., QTcF ≥ 470 msec)
- No situation or condition that would preclude study participation
- No known or suspected hypersensitivity to any excipients of lonafarnib (e.g.,
povidone, poloxamer 188, croscarmellose sodium, silicon dioxide, or magnesium
PRIOR CONCURRENT THERAPY:
- No prior or concurrent biologic therapy
- No prior or concurrent immunotherapy
- Prior adjuvant chemotherapy allowed provided the disease-free interval from
completion of treatment to diagnosis of advanced or metastatic disease is ≥ 12 months
- No prior chemotherapy for advanced disease
- No concurrent chemotherapy
- Prior adjuvant tamoxifen allowed provided the disease-free interval from completion
of treatment to diagnosis of advanced or metastatic disease is ≥ 12 months
- No prior hormonal therapy for advanced disease
- No prior aromatase inhibitors
- More than 2 days since prior and no concurrent high-dose chronic steroids
- No concurrent hormone replacement therapy
- No other concurrent hormonal therapy
- Prior radiotherapy allowed
- No concurrent radiotherapy except palliative radiotherapy for bone metastasis
- Not specified
- More than 30 days since prior investigational drugs
- No prior farnesyl transferase inhibitors
- More than 2 days since prior and no concurrent use of any of the following inducers
or inhibitors of CYP3A4:
- Ethinyl estradiol
- No concurrent participation in another clinical trial
- No other concurrent investigational therapy