Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer

PRIMARY OBJECTIVES:

I. To compare ixabepilone-induced peripheral neuropathy (sensory) as measured by European
Organization for Research and Treatment of Cancer (EORTC) Quality of life Questionnaire
(QLQ)-Chemotherapy-Induced Peripheral Neuropathy (CIPN)20 sensory subscale between calcium
(Ca) Magnesium (Mg) and placebo arms.

SECONDARY OBJECTIVES:

I. To compare the incidence of CTCAE measured grade 2+ and/or grade 3+ peripheral neuropathy
between CaMg and placebo arms.

II. To compare the times to onset of CTCAE measured grade 2+ and/or grade 3+ peripheral
neuropathy between CaMg and placebo arms.

III. To compare the proportion of patients requiring ixabepilone dose reductions and/or
stopping ixabepilone secondary to peripheral neuropathy (sensory) between CaMg and placebo
arms.

IV. To assess the toxicity of CaMg in this situation. V. To document the incidence and
severity of the acute pain syndrome (APS, commonly known as arthralgias/myalgias) induced by
ixabepilone.

VI. To evaluate whether CaMg will decrease the acute pain syndrome (APS). VII. To evaluate
the incidence and characteristics of, and change in, ixabepilone-APS over several cycles.

VIII. To evaluate the association between the ixabepilone-APS and eventual
chemotherapy-induced neuropathy.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes
immediately before and after each ixabepilone administration.

ARM II: Patients receive placebo IV over 30 minutes immediately before and after each
ixabepilone administration.

After completion of study treatment, patients are followed up monthly for 12 months.

Inclusion Criteria:

- Scheduled to undergo cancer treatment for metastatic breast cancer (weekly or once
every three weeks) with ixabepilone with no prior exposure to ixabepilone and no more
than 2 prior chemotherapy regimens for metastatic disease

- Serum calcium =< 1.2 x upper normal limit (UNL)

- Serum magnesium =< UNL

- Serum creatinine =< 1.5 x UNL

- Ability to sign informed consent and understand the nature of a placebo-controlled
trial

- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1, or 2

- Ability to complete questionnaire(s) by themselves or with assistance

- Life expectancy >= 4 months

- Presence of a central line

Exclusion Criteria:

- Pre-existing history of peripheral neuropathy >= grade 2 (National Cancer Institute
[NCI] CTCAE Active Version) due to any cause (chemotherapy, diabetes, alcohol, toxin,
hereditary, etc.)

- Concurrent treatment with anticonvulsants, tricyclic antidepressants, or other
neuropathic pain medications agents such as carbamazepine, phenytoin, valproic acid,
gabapentin, lamotrigine, topical lidocaine patch, capsaicin cream, etc., or any other
treatments specifically for prevention or treatment of neuropathy

- Other medical conditions, which in the opinion of the treating physician/allied
health professional would make this protocol unreasonably hazardous for the patient

- Any of the following:

- Pregnant women

- Nursing women

- Women of childbearing potential (per physician judgment)

- Diagnosed diabetes requiring insulin or oral hypoglycemic medications

- Receiving digoxin or digitoxin

- History of heart block (any degree)

- Current treatment for arrhythmias

- Concurrent treatment with other neuropathic chemotherapy agents