Official Title: “The Use of Calcium and Magnesium for Prevention of Ixabepilone Induced Peripheral Neuropathy: A Phase III Double-Blind Placebo Controlled Study”

RATIONALE : Giving calcium together with magnesium may stop or delay the development of peripheral neuropathy in patients with cancer who are receiving treatment with ixabepilone.

It is not yet known whether calcium and magnesium are more effective than a placebo in preventing peripheral neuropathy caused by ixabepilone. PURPOSE : This randomized phase III trial is studying calcium given together with magnesium to see how well it works compared with a placebo in preventing peripheral neuropathy caused by ixabepilone in patients with breast cancer.

Study Type: Interventional

Study Design: Supportive Care, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2015

PRIMARY OBJECTIVES: I. To compare ixabepilone-induced peripheral neuropathy (sensory) as measured by EORTC QLQ-CIPN20 sensory subscale between CaMg 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 ixabepilone treatment.

Arm II: Patients receive placebo IV over 30 minutes immediately before and after ixabepilone treatment. Treatment repeats every 7 or 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every month for up to 1 year.

Intervention(s) in this Clinical Trial

• Drug: calcium gluconate
  • Given IV
• Drug: magnesium sulfate
  • Given IV
• Other: placebo
  • Given IV
• Other: quality-of-life assessment
  • Correlative studies
• Other: questionnaire administration
  • Correlative studies
• Other: laboratory biomarker analysis
  • Correlative studies

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I
  • Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after ixabepilone treatment.
• Placebo Comparator: Arm II
  • Patients receive calcium placebo IV over 30 minutes immediately before and after ixabepilone treatment.

Primary Measures

• Comparison of chemotherapy-induced peripheral neuropathy between CaMg and placebo arms, as measured by the sensory subscale of EORTC QLQ-CIPN20
  • Time Frame: During the first 18 weeks of ixabepilone-based therapy
    Safety Issue?: No

Secondary Measures

• Percentage of patients with grade 2+ and/or grade 3+ neurotoxicity as measured by NCI-CTCAE v3.0 neuropathy scale
  • Safety Issue?: Yes
• Time to onset of grade 2+ and/or grade 3+ neurotoxicity as assessed by NCI-CTCAE v3.0
  • Safety Issue?: Yes
• Proportion of patients undergoing dose reduction or discontinuing ixabepilone secondary to peripheral neuropathy
  • Safety Issue?: No
• Average cumulative ixabepilone dose
  • Safety Issue?: No
• Toxicity profile of CaMg
  • Safety Issue?: Yes
• Incidence and severity of the acute pain syndrome (APS)
  • Time Frame: Over several courses
    Safety Issue?: No
• Association between the ixabepilone-APS and eventual chemotherapy-induced neuropathy
  • Safety Issue?: No

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
• Please contact study investigator and/or consult protocol document for specific details on laboratory criteria
• Ability to sign informed consent and understand the nature of a placebo-controlled trial
• 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 placed for administration of calcium and magnesium

Exclusion Criteria:

• Pre-existing history of peripheral neuropathy >= grade 2 (NCI CTCAE v 3.0) 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Mayo Clinic

Overall Clinical Trial Officials and Contacts

Charles Loprinzi Principal Investigator Mayo Clinic  

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00998738

Study ID Number: RC08CC

ClinicalTrials.gov Identifier: NCT00998738

Health Authority: United States: Institutional Review Board