Paricalcitol and Chemotherapy in Treating Women With Metastatic Breast Cancer

OBJECTIVES:

Primary

- To determine the ability to administer 8 continuous weeks of therapy within the first 3
months of enrollment with paricalcitol when given together with taxane or ixabepilone
therapy in women with metastatic breast cancer.

- To estimate the proportion of patients who successfully complete 8 continuous weeks of
therapy as well as the proportion of patients who achieve a 'steady-state' dose.

Secondary

- To determine a dose of paricalcitol that can be taken continuously that maintains a
normal calcium level when combined with a taxane or ixabepilone.

- To determine if baseline levels of 25-hydroxycholecalciferol and parathyroid hormone
(PTH) are associated with time to treatment failure in these patients.

- To determine if PTH levels decline from baseline in patients treated with paricalcitol
in combination with taxane or ixabepilone therapy.

OUTLINE: Beginning on day 1, patients receive oral paricalcitol. The dose of paricalcitol is
increased every 2 weeks until the serum calcium level is between 9 mg/dL and 11.4 mg/dL.
Once this level is reached, the patient continues at that dose for the duration of the
study. Patients also receive paclitaxel albumin-stabilized nanoparticle formulation,
docetaxel, or paclitaxel once a week or once every 3 weeks or ixabepilone once every 3
weeks. Treatment continues for at least 12 weeks in the absence of disease progression or
unacceptable toxicity.

Inclusion Criteria

- Histologically confirmed invasive breast cancer

- Metastatic or recurrent disease

- Patients with bone metastasis only are eligible and evaluable for time to
progression

- Candidate for taxane or ixabepilone therapy

- At least one lesion that can be measured in at least one diameter ≥ 2 cm by CT scan

- No symptomatic brain metastases or other symptomatic CNS metastases

- ECOG performance status 0 or 1

- Life expectancy > 3 months

- ANC ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9 g/dL

- Serum creatinine ≤ 2.0 mg/dL

- Total bilirubin ≤ 2.0 g/dL

- Albumin corrected serum calcium < 10.5 mg/dL

- Fertile patients must use effective contraception during and for at least 1 year
after study participation

- At least 2 weeks since prior chemotherapy or radiation therapy

- Prior and concurrent taxane or ixabepilone therapy allowed

- Concurrent oral multivitamins allowed (i.e., Centrum or One a Day)

- Concurrent bisphosphonates allowed

Exclusion Criteria

- History of allergy to calcitriol, paricalcitol, or other Vitamin D compounds

- History of drug or alcohol abuse within the past 6 months

- History of other malignancy except inactive nonmelanoma skin cancer, adequately
treated stage I or II cancer from which the patient is currently in complete
remission, or other cancer if the patient has been disease-free for 5 or more years

- Serious medical illness that would limit survival to < 3 months

- Active, uncontrolled bacterial, viral or fungal infection

- Poorly controlled diabetes

- Concurrent supplemental calcium

- Concurrent digitalis compounds

- Concurrent chemotherapy

- Concurrent biologic therapy, including trastuzumab and bevacizumab

- Concurrent hormonal agents for breast cancer except luteinizing hormone-releasing
hormone agonists