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

This study has been terminated.
(Study was terminated due to lack of accrual)
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00998738
First received: October 19, 2009
Last updated: July 26, 2013
Last verified: July 2013

October 19, 2009
July 26, 2013
November 2009
July 2010   (final data collection date for primary outcome 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 [ Time Frame: During the first 18 weeks of ixabepilone-based therapy ] [ Designated as safety issue: No ]
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) sensor subscale score was calculated following the standard scoring algorithm and was transformed to a 0 to 100 scale with 0=Low QOL and 100=Best QOL for data analysis.
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 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00998738 on ClinicalTrials.gov Archive Site
  • Percentage of Patients With Grade 2+ and/or Grade 3+ Neurotoxicity as Measured by NCI CTCAE Active Version Neuropathy Scale [ Time Frame: Up to 12 months from initiation of ixabepilone ] [ Designated as safety issue: Yes ]
  • Time to Onset of Grade 2+ and/or Grade 3+ Neurotoxicity as Assessed by NCI CTCAE Active Version [ Time Frame: Up to 12 months from initiation of ixabepilone ] [ Designated as safety issue: Yes ]
    Time to onset of grade 2+ neurotoxicity was defined as time from randomization to the first occurrence of grade 2+ neurotoxicity. Time to onset of grade 3+ neurotoxicity was defined as time from randomization to the first occurrence of grade 3+ neurotoxicity.
  • Proportion of Patients Undergoing Dose Reduction or Discontinuing Ixabepilone Secondary to Peripheral Neuropathy [ Time Frame: Up to 12 months from initiation of ixabepilone ] [ Designated as safety issue: No ]
  • Average Cumulative Ixabepilone Dose [ Time Frame: Up to 12 months from initiation of ixabepilone ] [ Designated as safety issue: No ]
  • Toxicity Profile of CaMg Per CTCAE Active Version [ Time Frame: Up to 12 months from initiation of ixabepilone ] [ Designated as safety issue: Yes ]
  • Incidence of the Acute Pain Syndrome (APS) [ Time Frame: Treatment initiation to day 21 (Cycle 1) ] [ Designated as safety issue: No ]

    APS was measured using the pain item which evaluated the aches/pains at its WORST in the last 24 hours in the scale of 0 to 10, with 0=no aches/pain and 10=aches/pains as bad as can be.

    The outcome measures for each subsequent cycle will be analyzed in a similar fashion.

  • Severity of the Acute Pain Syndrome (APS) [ Time Frame: Treatment initiation to day 21 (Cycle 1) ] [ Designated as safety issue: No ]

    APS was measured using the pain item which evaluated the aches/pains at its WORST in the last 24 hours in the scale of 0 to 10, with 0=no aches/pain and 10=aches/pains as bad as can be.

    The outcome measures for each subsequent cycle will be analyzed in a similar fashion.

  • Association Between the Ixabepilone-APS and Eventual Chemotherapy-induced Neuropathy [ Time Frame: First cycle of therapy (up to 21 days) ] [ Designated as safety issue: No ]
    Correlation coefficients will be produced relating the worst pain scores in the first cycle of therapy and the subsequent neuropathy scores as judged from the daily and weekly questions.
  • Percentage of patients with grade 2+ and/or grade 3+ neurotoxicity as measured by NCI-CTCAE v3.0 neuropathy scale [ Designated as safety issue: Yes ]
  • Time to onset of grade 2+ and/or grade 3+ neurotoxicity as assessed by NCI-CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Proportion of patients undergoing dose reduction or discontinuing ixabepilone secondary to peripheral neuropathy [ Designated as safety issue: No ]
  • Average cumulative ixabepilone dose [ Designated as safety issue: No ]
  • Toxicity profile of CaMg [ Designated as safety issue: Yes ]
  • Incidence and severity of the acute pain syndrome (APS) [ Time Frame: Over several courses ] [ Designated as safety issue: No ]
  • Association between the ixabepilone-APS and eventual chemotherapy-induced neuropathy [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
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.

PRIMARY OBJECTIVES:

To compare ixabepilone-induced peripheral neuropathy (sensory) as measured by European Organisation for Research and Treatment of Cancer 20-item module for chemotherapy-induced peripheral neuropathy (EORTC QLQ-CIPN20) sensory subscale between Calcium with Magnesium (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 each 3 week dose of ixabepilone treatment.

ARM II: Patients receive placebo IV over 30 minutes immediately before and after each 3 week dose of ixabepilone treatment.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
  • Stage IV Breast Cancer
  • Recurrent Breast Cancer
  • Drug: calcium gluconate
    Given IV
  • Drug: magnesium sulfate
    Given IV
  • Other: placebo
    Given IV
  • Experimental: Arm I
    Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after each 3 week dose of ixabepilone treatment.
    Interventions:
    • Drug: calcium gluconate
    • Drug: magnesium sulfate
  • Placebo Comparator: Arm II
    Patients receive placebo IV over 30 minutes immediately before and after each 3 week dose of ixabepilone treatment.
    Intervention: Other: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
1
November 2012
July 2010   (final data collection date for primary outcome measure)

Inclusion:

  • 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 UNL
  • Serum magnesium =< UNL
  • Serum creatinine =< 1.5 x UNL
  • Ability to sign informed consent and understand the nature of a placebo-controlled trial
  • ECOG Performance Status (PS) of 0, 1, or 2 (this form is on the Mayo Clinic Cancer Research Consortium (MCCRC) website https:/mccrc.mayo.edu/mccrc/forms/NonProtocolSpecificForms/)
  • 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
  • Please contact study investigator and/or consult protocol document for specific details on laboratory criteria

Exclusion:

  • Pre-existing history of peripheral neuropathy >= grade 2 (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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00998738
RC08CC, NCI-2009-01229, 08-008811, CA163-195
Yes
Charles Loprinzi, M.D., Mayo Clinic Cancer Center
Mayo Clinic
National Cancer Institute (NCI)
Principal Investigator: Charles Loprinzi, M.D. Mayo Clinic
Mayo Clinic
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP