Calcium Gluconate and Magnesium Sulfate 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
- Conditions
- Colorectal CancerNeurotoxicity
- Interventions
- Registration Number
- NCT00316914
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- 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).
Patients complete quality of life questionnaires on day 1, a symptom experience diary on days 2-5 of their chemotherapy regimen, and questionnaires at 1 and 3 months after completion of study treatment.
Blood samples are collected at baseline and tested for the GSTP1 gene.
After completion of study treatment, patients are followed for at least 3 months.
PROJECTED ACCRUAL: A total of 300 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 104
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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. Ca/Mg calcium gluconate 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. Ca/Mg magnesium sulfate 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.
- Primary Outcome Measures
Name Time Method Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event 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 Outcome Measures
Name Time Method Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event 127 days Adverse Events were measured using CTCAE V3.0.
Percentage of Patients With Acute Neuropathic Adverse Event 127 days Acute neuropathic toxicities were measured using the Symptom Experience Diary and supplemental quality of life questions in the scale of 0 (no symptom) to 10 (worst symptom). The item score was reversed and transformed into 0 (low QOL) to 100 (best QOL) scale for analysis. Any score greater than 0 was considered having acute neuropathy.
Time to Onset of Grade 2+ Chronic Neurotoxicity 127 days Neurotoxicity were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
Time to Onset of Grade 3+ Chronic Neurotoxicity 127 days Neurotoxicity was assessed by CTCAE v3.0.
Average Duration of Chronic Neuropathic Toxicity 127 days Neuropathic adverse events were assessed by CTCAE v3.0.
Percentage of Patients Discontinuing Therapy for Chronic Neurotoxicity 127 days Neurotoxicity were assessed by CTCAE v3.0.
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 Activities of daily living were measured using the Symptom Experience Diary and supplemental quality of life questions. The questionnaires' items were in the scale of 0 (no symptom) to 10 (worst symptom).
Change From Baseline in Fatigue Score at One Month Baseline and One month Fatigue was measured by Brief Fatigue Inventory in the scale of 0 (no fatigue) to 10 (fatigue as bad as you can imagine). The item score was reversed and transformed into 0 (low quality of life (QOL)) to 100 (best QOL) scale for analysis. Change: score at one month minus score at baseline.
Change From Baseline in Quality of Life (QOL) at One Month Baseline and One month Quality of Life (QOL) were measured using the Symptom Experience Diary and supplemental quality of life questions. Item score range: 0 (no symptom) to 10 (worst symptom). The score was reversed and transformed into 0 (low QOL) to 100 (best QOL) scale for analysis. Change: score at one month minus score at baseline.
Trial Locations
- Locations (14)
Medical Oncology and Hematology Associates at John Stoddard Cancer Center
🇺🇸Des Moines, Iowa, United States
Mercy Cancer Center at Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Mercy Capitol Hospital
🇺🇸Des Moines, Iowa, United States
John Stoddard Cancer Center at Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates at Mercy Cancer Center
🇺🇸Des Moines, Iowa, United States
MBCCOP - Medical College of Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
Bismarck Cancer Center
🇺🇸Bismarck, North Dakota, United States
Medcenter One Hospital Cancer Care Center
🇺🇸Bismarck, North Dakota, United States
Mid Dakota Clinic, PC
🇺🇸Bismarck, North Dakota, United States
John Stoddard Cancer Center at Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Sanford Cancer Center at Sanford USD Medical Center
🇺🇸Sioux Falls, South Dakota, United States
CCOP - Iowa Oncology Research Association
🇺🇸Des Moines, Iowa, United States
Medical X-Ray Center, PC
🇺🇸Sioux Falls, South Dakota, United States