Trial Outcomes & Findings for Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy (NCT NCT01099449)

Last Updated: 2022-11-03

Results Overview

The oxaliplatin-induced sensory neuropathy as repeatedly measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of Chemotherapy-induced peripheral neuropathy (EORTC QLQ-CIPN20) sensory subscale during the chemotherapy. This is a multivariate repeated measurement of CIPN with possibly variable cycles for every patient. The CIPN sensory subscale will be calculated by standard scoring algorithm and converted to 0-100 scale, where higher scores represent a higher quality of life. Rather than choosing the CIPN20 sensory subscale at a fixed cycle of chemotherapy, we will adopt a summary measure, area under the curve (AUC) of CIPN20 sensory subscale as the primary endpoint. This AUC will be prorated by the number of chemotherapy cycles patients received.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

362 participants

Primary outcome timeframe

Up to 18 months

Results posted on

2022-11-03

Participant Flow

Participant milestones

Participant milestones
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).	Placebo (Pre and Post) Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).
Overall Study STARTED	118	119	116
Overall Study COMPLETED	118	119	116
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=118 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\>\> \>\> calcium gluconate: Given IV\>\> \>\> magnesium sulfate: Given IV\>\> \>\> oxaliplatin	Placebo (Pre and Post) n=119 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\>\> \>\> placebo: Given IV\>\> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=116 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\>\> \>\> calcium gluconate: Given IV\>\> \>\> magnesium sulfate: Given IV\>\> \>\> placebo: Given IV\>\> \>\> \>\> \>\>\> oxaliplatin	Total n=353 Participants Total of all reporting groups
Age, Continuous	57 years n=5 Participants	56 years n=7 Participants	57 years n=5 Participants	56 years n=4 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	62 Participants n=7 Participants	60 Participants n=5 Participants	184 Participants n=4 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	57 Participants n=7 Participants	56 Participants n=5 Participants	169 Participants n=4 Participants
Region of Enrollment Ecuador	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	118 Participants n=5 Participants	118 Participants n=7 Participants	116 Participants n=5 Participants	352 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 18 months

Population: All enrolled patients with Baseline and more than 1 cycle of Sensory data.

Outcome measures

Outcome measures
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=110 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> oxaliplatin	Placebo (Pre and Post) n=106 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=110 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin
Sensory Area Under the Curve(AUC) Score. Oxaliplatin-induced Sensory Neuropathy as Repeatedly Measured by the EORTC QLQ-CIPN20 Sensory Subscale During Chemotherapy	89.2 score on a scale Standard Deviation 8.5	88.3 score on a scale Standard Deviation 9.7	87.1 score on a scale Standard Deviation 9.9

SECONDARY outcome

Timeframe: Up to 18 months

Population: All patients with Baseline and more than one cycle of EORTC CIPN-20 Autonomic data.

The oxaliplatin-induced autonomic neuropathy as repeatedly measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of Chemotherapy-induced peripheral neuropathy (EORTC QLQ-CIPN20) autonomic subscale during the chemotherapy. This is a multivariate repeated measurement of CIPN with possibly variable cycles for every patient. The CIPN autonomic subscale will be calculated by standard scoring algorithm and converted to 0-100 scale, where higher scores represent a higher quality of life. Rather than choosing the CIPN20 autonomic subscale at a fixed cycle of chemotherapy, we will adopt a summary measure, area under the curve (AUC) of CIPN20 autonomic subscale as the endpoint. This AUC will be prorated by the number of chemotherapy cycles patients received.

Outcome measures

Outcome measures
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=108 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> oxaliplatin	Placebo (Pre and Post) n=102 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=111 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin
Area Under the Curve (AUC) of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of Chemotherapy-induced Peripheral Neuropathy (EORTC QLQ-CIPN20) Autonomic Neuropathy Subscale Scores	89.8 score on a scale Standard Deviation 12.5	86.7 score on a scale Standard Deviation 14.3	84.5 score on a scale Standard Deviation 15.1

SECONDARY outcome

Timeframe: Up to 18 Months

Population: All patients with at least baseline and more than 1 cycle of Motor Neuropathy data.

The oxaliplatin-induced motor neuropathy as repeatedly measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of Chemotherapy-induced peripheral neuropathy (EORTC QLQ-CIPN20) motor neuropathy subscale during the chemotherapy. This is a multivariate repeated measurement of CIPN with possibly variable cycles for every patient. The CIPN motor neuropathy subscale will be calculated by standard scoring algorithm and converted to 0-100 scale, where higher scores represent a higher quality of life. Rather than choosing the CIPN20 motor neuropathy subscale at a fixed cycle of chemotherapy, we will adopt a summary measure, area under the curve (AUC) of CIPN20 motor neuropathy subscale as the endpoint. This AUC will be prorated by the number of chemotherapy cycles patients received.

Outcome measures

Outcome measures
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=110 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> oxaliplatin	Placebo (Pre and Post) n=106 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=110 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin
Area Under the Curve (AUC) of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of Chemotherapy-induced Peripheral Neuropathy (EORTC QLQ-CIPN20) Motor Neuropathy Subscale Scores	94.1 AUC QLQ-CIPN20 Motor Neuropathy Score Standard Deviation 7.9	93.3 AUC QLQ-CIPN20 Motor Neuropathy Score Standard Deviation 8.0	91.6 AUC QLQ-CIPN20 Motor Neuropathy Score Standard Deviation 10.5

SECONDARY outcome

Timeframe: Up to 18 months

Population: All patients that under went at least one cycle of treatment and were analyzed for chronic cumulative neurotoxicity (NCI CTCAE version 4.0 and oxaliplatin-specific neurotoxicity scale) during and after chemotherapy

Grades are determined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.0) and oxaliplatin-specific neurotoxicity scale, during and after chemotherapy. Higher grades symbolize greater severity of the adverse event.

Outcome measures

Outcome measures
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=118 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> oxaliplatin	Placebo (Pre and Post) n=119 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=116 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin
Percentage of Patients Experiencing Grade 2+ and Grade 3+ Chronic Cumulative Neurotoxicity. grade 2+	42.7 percentage of patients	44.8 percentage of patients	46.1 percentage of patients
Percentage of Patients Experiencing Grade 2+ and Grade 3+ Chronic Cumulative Neurotoxicity. grade 3+	7.7 percentage of patients	7.8 percentage of patients	7.8 percentage of patients

SECONDARY outcome

Timeframe: Up to 18 months

Time to onset of grade 2+ and grade 3+ chronic cumulative neurotoxicity, the duration of the chronic cumulative neurotoxicity during and after the adjuvant oxaliplatin-based chemotherapy. Grades are determined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.0) and oxaliplatin-specific neurotoxicity scale, during and after chemotherapy. Higher grades symbolize greater severity of the adverse event.

Outcome measures

Outcome measures
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=109 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> oxaliplatin	Placebo (Pre and Post) n=108 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=105 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin
Time to Onset of Grade 2+ and Grade 3+ Chronic Cumulative Neurotoxicity and the Duration of the Chronic Cumulative Neurotoxicity During and After Chemotherapy Time to Grade 2 Neuropathy	171 Days Interval 154.0 to 190.0	173 Days Interval 162.0 to 181.0	171 Days Interval 148.0 to 173.0
Time to Onset of Grade 2+ and Grade 3+ Chronic Cumulative Neurotoxicity and the Duration of the Chronic Cumulative Neurotoxicity During and After Chemotherapy Time to Grade 3 Neuropathy	NA Days Interval 209.0 to Not Reached	208 Days Interval 200.0 to Not Reached	NA Days Interval 201.0 to Not Reached

SECONDARY outcome

Timeframe: Up to 18 months

Population: All patients that discontinued treatment.

A patient has a dose-limiting chronic neurotoxicity when they discontinue oxaliplatin-based chemotherapy because of neurotoxicity.

Outcome measures

Outcome measures
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=34 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> oxaliplatin	Placebo (Pre and Post) n=32 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=28 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin
Cumulative Oxaliplatin Doses That Can be Administered Without Dose-limiting Chronic Neurotoxicity	8.1 Doses Standard Deviation 3	8.4 Doses Standard Deviation 2.5	8.0 Doses Standard Deviation 2.6

SECONDARY outcome

Timeframe: Up to 18 months

Population: All patients that received treatment.

Outcome measures

Outcome measures
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=118 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> oxaliplatin	Placebo (Pre and Post) n=119 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=116 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin
Percentage of Patients Discontinuing Oxaliplatin-based Chemotherapy Because of Neurotoxicity	34.7 percentage of patients	27.7 percentage of patients	30.5 percentage of patients

SECONDARY outcome

Timeframe: Up to 18 months

This is the percent of patients who scored \>=50 in all sequences of all cycles by arm for side effect Q1: Sensitivity to touching cold. This is a\> repeated measurement of CIPN with possibly variable cycles for every patient. The CIPN subscale will be calculated by standard scoring algorithm and converted to 0-100 scale. Where 0 is no sensitivity and 100 is as bad as it can be.

Outcome measures

Outcome measures
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=110 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> oxaliplatin	Placebo (Pre and Post) n=106 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=110 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 7	35 percentage of patients	34 percentage of patients	34 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 1	10 percentage of patients	13 percentage of patients	14 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 2	24 percentage of patients	27 percentage of patients	28 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 3	32 percentage of patients	33 percentage of patients	32 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 4	34 percentage of patients	37 percentage of patients	36 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 5	34 percentage of patients	33 percentage of patients	39 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 6	31 percentage of patients	37 percentage of patients	33 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 8	32 percentage of patients	34 percentage of patients	33 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 9	34 percentage of patients	37 percentage of patients	32 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 10	29 percentage of patients	39 percentage of patients	30 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 11	28 percentage of patients	39 percentage of patients	33 percentage of patients
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Cycle 12	27 percentage of patients	45 percentage of patients	32 percentage of patients

SECONDARY outcome

Timeframe: Up to 18 months

Outcome measures

Outcome measures
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=118 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> oxaliplatin	Placebo (Pre and Post) n=119 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=116 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin
Incidence of Calcium Gluconate and Magnesium Sulfate-induced Adverse Events as Measured by CTCAE Version 4.0	290 Number of reported Adverse Events	259 Number of reported Adverse Events	296 Number of reported Adverse Events

SECONDARY outcome

Timeframe: Up to 18 months

Population: All patients that had at least one cycle of treatment and submitted a patient-reported quality of life (QOL) as measured by the supplemental QOL questionnaire

This is a multivariate repeated measurement of CIPN with possibly variable cycles for every patient. The supplemental quality of life (QOL) subscale will be calculated by standard scoring algorithm and converted to 0-100 scale, where higher scores represent a higher quality of life. Rather than choosing the subscale at a fixed cycle of chemotherapy, we will adopt a summary measure, area under the curve (AUC) . This AUC will be prorated by the number of chemotherapy cycles patients received.

Outcome measures

Outcome measures
Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=111 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> oxaliplatin	Placebo (Pre and Post) n=112 Participants Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=108 Participants Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).\> \>\> \> \>\> calcium gluconate: Given IV\> \>\> \> \>\> magnesium sulfate: Given IV\> \>\> \> \>\> placebo: Given IV\> \>\> \> \>\> oxaliplatin
Area Under the Curve (AUC) of Patient-reported Quality of Life (QOL) as Measured by the Supplemental QOL Questionnaire Tingling in finger and toes	78.9 score on a scale Standard Deviation 16.5	76.5 score on a scale Standard Deviation 17.3	76.3 score on a scale Standard Deviation 17.6
Area Under the Curve (AUC) of Patient-reported Quality of Life (QOL) as Measured by the Supplemental QOL Questionnaire Diarrhea	86.7 score on a scale Standard Deviation 15.5	86.2 score on a scale Standard Deviation 15.7	84.5 score on a scale Standard Deviation 16
Area Under the Curve (AUC) of Patient-reported Quality of Life (QOL) as Measured by the Supplemental QOL Questionnaire Constipation	90.1 score on a scale Standard Deviation 13.0	88.8 score on a scale Standard Deviation 13.4	88.0 score on a scale Standard Deviation 18.8
Area Under the Curve (AUC) of Patient-reported Quality of Life (QOL) as Measured by the Supplemental QOL Questionnaire Stomach Cramping	92.8 score on a scale Standard Deviation 11.4	90.6 score on a scale Standard Deviation 12.6	89.4 score on a scale Standard Deviation 15.6
Area Under the Curve (AUC) of Patient-reported Quality of Life (QOL) as Measured by the Supplemental QOL Questionnaire Bowel Problems	89.1 score on a scale Standard Deviation 13.4	88.5 score on a scale Standard Deviation 14.4	84.6 score on a scale Standard Deviation 19.0
Area Under the Curve (AUC) of Patient-reported Quality of Life (QOL) as Measured by the Supplemental QOL Questionnaire Swallowing	91.2 score on a scale Standard Deviation 10.0	87.6 score on a scale Standard Deviation 13.8	86.7 score on a scale Standard Deviation 14.1
Area Under the Curve (AUC) of Patient-reported Quality of Life (QOL) as Measured by the Supplemental QOL Questionnaire Numbness in finger and toes	83.4 score on a scale Standard Deviation 14.8	81.8 score on a scale Standard Deviation 15.7	80.0 score on a scale Standard Deviation 17.3

Adverse Events

Calcium Gluconate + Magnesium Sulfate (Pre and Post)

Serious events: 13 serious events

Other events: 107 other events

Deaths: 0 deaths

Placebo (Pre and Post)

Serious events: 9 serious events

Other events: 108 other events

Deaths: 0 deaths

Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post)

Serious events: 8 serious events

Other events: 105 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Charles Loprinzi, M.D.

Mayo Clinic

Phone: (507) 284-3731

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Calcium Gluconate + Magnesium Sulfate (Pre and Post) n=117 participants at risk oxaliplatin	Placebo (Pre and Post) n=119 participants at risk oxaliplatin	Calcium Gluconate + Magnesium Sulfate (Pre), Placebo (Post) n=116 participants at risk oxaliplatin
Blood and lymphatic system disorders Febrile neutropenia	0.85% 1/117 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.84% 1/119 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Cardiac disorders Atrial flutter	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.86% 1/116 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Gastrointestinal disorders Abdominal pain	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.86% 1/116 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Gastrointestinal disorders Constipation	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.86% 1/116 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Gastrointestinal disorders Diarrhea	7.7% 9/117 • Number of events 13 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	2.5% 3/119 • Number of events 3 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	2.6% 3/116 • Number of events 3 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Gastrointestinal disorders Nausea	2.6% 3/117 • Number of events 5 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	2.6% 3/116 • Number of events 6 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.86% 1/116 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Gastrointestinal disorders Vomiting	0.85% 1/117 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.86% 1/116 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
General disorders Fatigue	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.86% 1/116 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
General disorders Fever	0.85% 1/117 • Number of events 2 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Infections and infestations Abdominal infection	0.85% 1/117 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Infections and infestations Bronchial infection	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.84% 1/119 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Infections and infestations Urinary tract infection	0.85% 1/117 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Injury, poisoning and procedural complications Infusion related reaction	1.7% 2/117 • Number of events 2 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Investigations Alkaline phosphatase increased	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.84% 1/119 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Investigations Neutrophil count decreased	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	2.5% 3/119 • Number of events 4 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.86% 1/116 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Investigations Platelet count decreased	0.85% 1/117 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Metabolism and nutrition disorders Hypokalemia	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/119 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.86% 1/116 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.84% 1/119 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Nervous system disorders Transient ischemic attacks	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.84% 1/119 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Psychiatric disorders Anxiety	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.84% 1/119 • Number of events 5 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/117 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.84% 1/119 • Number of events 1 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).	0.00% 0/116 • 3 years This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 for adverse event monitoring and reporting. The CTCAE version 4.0 can be accessed from the CTEP home page (http://ctep.cancer.gov).