A Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 104
- Locations
- 14
- Primary Endpoint
- Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event
Study Overview
Brief Summary
RATIONALE: Calcium gluconate and magnesium sulfate may prevent or lessen neurotoxicity caused by oxaliplatin. It is not yet known whether calcium gluconate and magnesium sulfate are more effective than a placebo in preventing neurotoxicity caused by oxaliplatin in patients receiving combination chemotherapy.
PURPOSE: This randomized phase III trial is studying calcium gluconate and magnesium sulfate to see how well they work compared to a placebo in preventing neurotoxicity caused by oxaliplatin in patients receiving combination chemotherapy for stage II, stage III, or stage IV colorectal cancer that has been completely removed by surgery.
Detailed Description
OBJECTIVES:
- Determine whether calcium gluconate and magnesium sulfate (CaMg) infusions can prevent or ameliorate chronic, cumulative oxaliplatin-induced neurotoxicity in patients receiving FOLFOX combination chemotherapy for stage II, III or IV colorectal cancer.
- Determine whether CaMg infusions can increase the cumulative oxaliplatin doses that can be delivered without chronic neurotoxicity.
- Determine whether CaMg infusions can ameliorate the acute neuropathy associated with oxaliplatin.
- Determine whether CaMg infusions cause any adverse events.
- Investigate whether CaMg infusions influence quality of life, fatigue, and activities of daily living of these patients.
- Determine if polymorphisms in the GSTP1 gene predict early onset of oxaliplatin-induced neurotoxicity.
OUTLINE: This is a randomized, placebo-controlled, double-blind, multicenter study. Patients are stratified according to age (< 65 vs > 65), gender, and chemotherapy regimen (FOLFOX4 vs modified FOLFOX6). 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 oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.
- Arm II: Patients receive a placebo IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.
In both arms, treatment continues until chemotherapy is discontinued (approximately 6 months).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Supportive Care
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Ca/Mg
Patients receive calcium gluconate (Ca) and magnesium sulfate (Mg) IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.
Intervention: calcium gluconate (Drug)
Ca/Mg
Patients receive calcium gluconate (Ca) and magnesium sulfate (Mg) IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.
Intervention: magnesium sulfate (Drug)
Placebo
Patients receive a placebo IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.
Intervention: placebo (Other)
Outcomes
Primary Outcomes
Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event
Time Frame: 127 days
Neuropathic adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Neurotoxicity evaluation grade: loss of deep tendon reflexes or paresthesia, including tingling, but not interfering with function (Grade 1); objective sensory alteration or paresthesia, including tingling, interfering with function, but not with activities of daily living (Grade 2); sensory alteration or paresthesia interfering with activities of daily living (Grade 3); permanent sensory losses that are disabling (Grade 4)
Secondary Outcomes
- Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event(127 days)
- Percentage of Patients With Acute Neuropathic Adverse Event(127 days)
- Time to Onset of Grade 2+ Chronic Neurotoxicity(127 days)
- Time to Onset of Grade 3+ Chronic Neurotoxicity(127 days)
- Average Duration of Chronic Neuropathic Toxicity(127 days)
- Percentage of Patients Discontinuing Therapy for Chronic Neurotoxicity(127 days)
- Average Cumulative Oxaliplatin Dose(127 days)
- Average Duration of Oxaliplatin-containing Treatment(127 days)
- Percentage of Patients Experiencing Impact on Activities of Daily Living (ADL)(127 days)
- Change From Baseline in Fatigue Score at One Month(Baseline and One month)
- Change From Baseline in Quality of Life (QOL) at One Month(Baseline and One month)