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

This study has been terminated.
(lack of accrual)
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00998738
First received: October 19, 2009
Last updated: January 7, 2016
Last verified: November 2015

October 19, 2009
January 7, 2016
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
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
  • Neuropathy
  • Pain
  • Recurrent Breast Carcinoma
  • Stage IV Breast Cancer
  • Drug: Calcium Gluconate
    Given IV
    Other Names:
    • Calcium D-gluconate
    • Calglucon
  • Drug: Magnesium Sulfate
    Given IV
    Other Names:
    • Magnesium SO4
    • Magnesium Sulfate whiskers
  • Other: Placebo
    Given IV
    Other Names:
    • placebo therapy
    • PLCB
    • sham therapy
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
  • Drug: Ixabepilone
    Given IV
    Other Name: IXEMPRA
  • Experimental: Arm I (calcium gluconate, magnesium sulfate)
    Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after each ixabepilone administration.
    Interventions:
    • Drug: Calcium Gluconate
    • Drug: Magnesium Sulfate
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Drug: Ixabepilone
  • Placebo Comparator: Arm II (placebo)
    Patients receive placebo IV over 30 minutes immediately before and after each ixabepilone administration.
    Interventions:
    • Other: Placebo
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Drug: Ixabepilone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
1
January 2013
July 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00998738
RC08CC, NCI-2009-01229, RC08CC, P30CA015083
Yes
Not Provided
Not Provided
Mayo Clinic
Mayo Clinic
National Cancer Institute (NCI)
Principal Investigator: Charles Loprinzi Mayo Clinic
Mayo Clinic
November 2015

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