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
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ClinicalTrials.gov Identifier: NCT00316914 |
Recruitment Status
:
Completed
First Posted
: April 21, 2006
Results First Posted
: March 25, 2013
Last Update Posted
: August 11, 2016
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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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Colorectal Cancer Neurotoxicity | Drug: calcium gluconate Drug: magnesium sulfate Other: placebo | Phase 3 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 104 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Supportive Care |
Official Title: | A Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity |
Study Start Date : | January 2006 |
Actual Primary Completion Date : | January 2008 |
Actual Study Completion Date : | November 2012 |

Arm | Intervention/treatment |
---|---|
Experimental: 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.
|
Drug: calcium gluconate
Given IV
Drug: magnesium sulfate
Given IV
|
Placebo Comparator: 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.
|
Other: placebo
Given IV
|
- 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)
- Time to Onset of Grade 2+ Chronic Neurotoxicity [ Time Frame: 127 days ]Neurotoxicity were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
- Time to Onset of Grade 3+ Chronic Neurotoxicity [ Time Frame: 127 days ]Neurotoxicity was assessed by CTCAE v3.0.
- Average Duration of Chronic Neuropathic Toxicity [ Time Frame: 127 days ]Neuropathic adverse events were assessed by CTCAE v3.0.
- Percentage of Patients Discontinuing Therapy for Chronic Neurotoxicity [ Time Frame: 127 days ]Neurotoxicity were assessed by CTCAE v3.0.
- Average Cumulative Oxaliplatin Dose [ Time Frame: 127 days ]
- Average Duration of Oxaliplatin-containing Treatment [ Time Frame: 127 days ]
- Percentage of Patients With Acute Neuropathic Adverse Event [ Time Frame: 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.
- Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event [ Time Frame: 127 days ]Adverse Events were measured using CTCAE V3.0.
- Percentage of Patients Experiencing Impact on Activities of Daily Living (ADL) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
-
Histologically confirmed adenocarcinoma of the colon or rectum
- Stage II disease
- Stage III disease
- Stage IV disease (completely resected with no evidence of residual tumor)
- Must have undergone curative resection for stage II or III disease
-
Scheduled to receive 6 months of adjuvant treatment with either of the following FOLFOX chemotherapy regimens:
- FOLFOX4, comprising leucovorin calcium, fluorouracil, and oxaliplatin (2-week course)
- Modified FOLFOX6, comprising high-dose leucovorin calcium, high-dose fluorouracil, and oxaliplatin (2-week course)
PATIENT CHARACTERISTICS:
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10 g/dL
- WBC ≥ 3,000/mm^3
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- Creatinine ≤ 1.5 times ULN
- Calcium normal
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No pre-existing peripheral neuropathy of any grade
- No hypercalcemia
- No concurrent heart block or a history of heart block
- No other medical condition that, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
- No family history of a genetic/familial neuropathy
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior treatment with neurotoxic chemotherapy such as oxaliplatin, cisplatin, taxanes, or vinca alkaloids
- Concurrent use of bevacizumab or cetuximab in combination with FOLFOX as part of a clinical trial or clinical practice are allowed
- No concurrent digitalis medication
- No concurrent digoxin
- No concurrent treatment with anticonvulsants such as carbamazepine, phenytoin, or valproic acid
- No other concurrent neurotropic agents such as gabapentin

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00316914
United States, Georgia | |
MBCCOP - Medical College of Georgia Cancer Center | |
Augusta, Georgia, United States, 30912 | |
United States, Iowa | |
Mercy Capitol Hospital | |
Des Moines, Iowa, United States, 50307 | |
CCOP - Iowa Oncology Research Association | |
Des Moines, Iowa, United States, 50309 | |
John Stoddard Cancer Center at Iowa Methodist Medical Center | |
Des Moines, Iowa, United States, 50309 | |
Medical Oncology and Hematology Associates at John Stoddard Cancer Center | |
Des Moines, Iowa, United States, 50309 | |
Medical Oncology and Hematology Associates at Mercy Cancer Center | |
Des Moines, Iowa, United States, 50314 | |
Mercy Cancer Center at Mercy Medical Center - Des Moines | |
Des Moines, Iowa, United States, 50314 | |
John Stoddard Cancer Center at Iowa Lutheran Hospital | |
Des Moines, Iowa, United States, 50316 | |
United States, North Dakota | |
Bismarck Cancer Center | |
Bismarck, North Dakota, United States, 58501 | |
Medcenter One Hospital Cancer Care Center | |
Bismarck, North Dakota, United States, 58501 | |
Mid Dakota Clinic, PC | |
Bismarck, North Dakota, United States, 58501 | |
United States, South Dakota | |
Avera Cancer Institute | |
Sioux Falls, South Dakota, United States, 57105 | |
Medical X-Ray Center, PC | |
Sioux Falls, South Dakota, United States, 57105 | |
Sanford Cancer Center at Sanford USD Medical Center | |
Sioux Falls, South Dakota, United States, 57117-5039 |
Study Chair: | Axel Grothey, MD | Mayo Clinic |
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Alliance for Clinical Trials in Oncology |
ClinicalTrials.gov Identifier: | NCT00316914 History of Changes |
Other Study ID Numbers: |
NCCTG-N04C7 CDR0000471238 ( Registry Identifier: NCI Physician Data Query ) |
First Posted: | April 21, 2006 Key Record Dates |
Results First Posted: | March 25, 2013 |
Last Update Posted: | August 11, 2016 |
Last Verified: | July 2016 |
Keywords provided by Alliance for Clinical Trials in Oncology:
neurotoxicity stage II colon cancer stage III colon cancer adenocarcinoma of the colon stage II rectal cancer |
stage III rectal cancer stage IV rectal cancer stage IV colon cancer adenocarcinoma of the rectum |
Additional relevant MeSH terms:
Neurotoxicity Syndromes Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Nervous System Diseases Poisoning Chemically-Induced Disorders |
Calcium, Dietary Oxaliplatin Magnesium Sulfate Bone Density Conservation Agents Physiological Effects of Drugs Antineoplastic Agents Analgesics Sensory System Agents Peripheral Nervous System Agents Anesthetics Central Nervous System Depressants Anti-Arrhythmia Agents Anticonvulsants Calcium Channel Blockers Membrane Transport Modulators |