Clinical trial NCT00998738: Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
Official title: The Use of Calcium and Magnesium for Prevention of Ixabepilone Induced Peripheral Neuropathy: A Phase III Double-Blind Placebo Controlled Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Neuropathy
Pain
Recurrent Breast Carcinoma
Stage IV Breast Cancer
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-10-20
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This randomized phase III trial studies calcium and magnesium to see how well they work in preventing peripheral neuropathy caused by ixabepilone in patients with breast cancer. 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 effective in preventing peripheral neuropathy caused by ixabepilone.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Comparison of Chemotherapy-induced Peripheral Neuropathy Between Calcium With Magnesium (CaMg) and Placebo Arms, as Measured by the Sensory Subscale of EORTC QLQ-CIPN20
timeFrame: During the first 18 weeks of ixabepilone-based therapy
Secondary outcomes:
measure: Percentage of Patients With Grade 2+ and/or Grade 3+ Neurotoxicity as Measured by NCI CTCAE Active Version Neuropathy Scale
timeFrame: Up to 12 months from initiation of ixabepilone
measure: Time to Onset of Grade 2+ and/or Grade 3+ Neurotoxicity as Assessed by NCI CTCAE Active Version
timeFrame: Up to 12 months from initiation of ixabepilone
measure: Proportion of Patients Undergoing Dose Reduction or Discontinuing Ixabepilone Secondary to Peripheral Neuropathy
timeFrame: Up to 12 months from initiation of ixabepilone
measure: Average Cumulative Ixabepilone Dose
timeFrame: Up to 12 months from initiation of ixabepilone
measure: Toxicity Profile of CaMg Per CTCAE Active Version
timeFrame: Up to 12 months from initiation of ixabepilone
measure: Incidence of the Acute Pain Syndrome (APS)
timeFrame: Treatment initiation to day 21 (Cycle 1)
measure: Severity of the Acute Pain Syndrome (APS)
timeFrame: Treatment initiation to day 21 (Cycle 1)
measure: Association Between the Ixabepilone-APS and Eventual Chemotherapy-induced Neuropathy
timeFrame: First cycle of therapy (up to 21 days)
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Charles Loprinzi
role: PRINCIPAL_INVESTIGATOR
References: