Neuropathy, Pain, Recurrent Breast Carcinoma, Stage IV Breast Cancer
Conditions
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.
Interventions
Given IV
DRUGMagnesium Sulfate
Given IV
OTHERPlacebo
Given IV
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
DRUGIxabepilone
Given IV
Sponsors
National Cancer Institute (NCI)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Chemotherapy-induced Peripheral Neuropathy Between Calcium With Magnesium (CaMg) and Placebo Arms, as Measured by the Sensory Subscale of EORTC QLQ-CIPN20 | During the first 18 weeks of ixabepilone-based therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Grade 2+ and/or Grade 3+ Neurotoxicity as Assessed by NCI CTCAE Active Version | Up to 12 months from initiation of ixabepilone | 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 | Up to 12 months from initiation of ixabepilone | — |
| Average Cumulative Ixabepilone Dose | Up to 12 months from initiation of ixabepilone | — |
| Percentage of Patients With Grade 2+ and/or Grade 3+ Neurotoxicity as Measured by NCI CTCAE Active Version Neuropathy Scale | Up to 12 months from initiation of ixabepilone | — |
| Incidence of the Acute Pain Syndrome (APS) | Treatment initiation to day 21 (Cycle 1) | 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) | Treatment initiation to day 21 (Cycle 1) | 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 | First cycle of therapy (up to 21 days) | 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. |
| Toxicity Profile of CaMg Per CTCAE Active Version | Up to 12 months from initiation of ixabepilone | — |
Countries
United States
Participant flow
Recruitment details
One participant was recruited between November 2009 and July 2010 at Mayo Clinic. This trial was terminated in July 2010 due to lack of accrual. Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.
Participants by arm
| Arm | Count |
|---|---|
| Overall | 0 |
| Total | 0 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Uknown | 1 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | — Participants |
| Age, Categorical >=65 years | — Participants |
| Age, Categorical Between 18 and 65 years | — Participants |
| Region of Enrollment United States | — participants |
| Sex: Female, Male Female | — Participants |
| Sex: Female, Male Male | — Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Comparison of Chemotherapy-induced Peripheral Neuropathy Between Calcium With Magnesium (CaMg) and Placebo Arms, as Measured by the Sensory Subscale of EORTC QLQ-CIPN20
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.
Time frame: During the first 18 weeks of ixabepilone-based therapy
Population: Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.
Secondary
Association Between the Ixabepilone-APS and Eventual Chemotherapy-induced Neuropathy
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.
Time frame: First cycle of therapy (up to 21 days)
Population: Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.
Secondary
Average Cumulative Ixabepilone Dose
Time frame: Up to 12 months from initiation of ixabepilone
Population: Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.
Secondary
Incidence of the Acute Pain Syndrome (APS)
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.
Time frame: Treatment initiation to day 21 (Cycle 1)
Population: Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.
Secondary
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
Population: Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.
Secondary
Proportion of Patients Undergoing Dose Reduction or Discontinuing Ixabepilone Secondary to Peripheral Neuropathy
Time frame: Up to 12 months from initiation of ixabepilone
Population: Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.
Secondary
Severity of the Acute Pain Syndrome (APS)
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.
Time frame: Treatment initiation to day 21 (Cycle 1)
Population: Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.
Secondary
Time to Onset of Grade 2+ and/or Grade 3+ Neurotoxicity as Assessed by NCI CTCAE Active Version
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.
Time frame: Up to 12 months from initiation of ixabepilone
Population: Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.
Secondary
Toxicity Profile of CaMg Per CTCAE Active Version
Time frame: Up to 12 months from initiation of ixabepilone
Population: Since only one patient was accrued, patient confidentiality prevents the reporting of this patient.