- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00316914
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
A Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Georgia
-
Augusta, Georgia, United States, 30912
- MBCCOP - Medical College of Georgia Cancer Center
-
-
Iowa
-
Des Moines, Iowa, United States, 50309
- 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, 50314
- 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, 50316
- John Stoddard Cancer Center at Iowa Lutheran Hospital
-
Des Moines, Iowa, United States, 50307
- Mercy Capitol Hospital
-
-
North Dakota
-
Bismarck, North Dakota, United States, 58501
- 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
-
-
South Dakota
-
Sioux Falls, South Dakota, United States, 57105
- Avera Cancer Institute
-
Sioux Falls, South Dakota, United States, 57105
- Medical X-Ray Center, PC
-
Sioux Falls, South Dakota, United States, 57117-5039
- Sanford Cancer Center at Sanford USD Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / 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.
|
Given IV
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.
|
Given IV
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
127 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
127 days
|
Time to Onset of Grade 3+ Chronic Neurotoxicity
Time Frame: 127 days
|
Neurotoxicity was assessed by CTCAE v3.0.
|
127 days
|
Average Duration of Chronic Neuropathic Toxicity
Time Frame: 127 days
|
Neuropathic adverse events were assessed by CTCAE v3.0.
|
127 days
|
Percentage of Patients Discontinuing Therapy for Chronic Neurotoxicity
Time Frame: 127 days
|
Neurotoxicity were assessed by CTCAE v3.0.
|
127 days
|
Average Cumulative Oxaliplatin Dose
Time Frame: 127 days
|
127 days
|
|
Average Duration of Oxaliplatin-containing Treatment
Time Frame: 127 days
|
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.
|
127 days
|
Incidence of Calcium Magnesium (CaMg)-Induced Adverse Event
Time Frame: 127 days
|
Adverse Events were measured using CTCAE V3.0.
|
127 days
|
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).
|
127 days
|
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.
|
Baseline and One month
|
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.
|
Baseline and One month
|
Collaborators and Investigators
Publications and helpful links
General Publications
- Grothey A, Nikcevich DA, Sloan JA, Kugler JW, Silberstein PT, Dentchev T, Wender DB, Novotny PJ, Chitaley U, Alberts SR, Loprinzi CL. Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in adjuvant colon cancer: NCCTG N04C7. J Clin Oncol. 2011 Feb 1;29(4):421-7. doi: 10.1200/JCO.2010.31.5911. Epub 2010 Dec 28.
- Nikcevich DA, Grothey A, Sloan JA, et al.: Effect of intravenous calcium and magnesium (IV CaMg) on oxaliplatin-induced sensory neurotoxicity (sNT) in adjuvant colon cancer: results of the phase III placebo-controlled, double-blind NCCTG trial N04C7. [Abstract] J Clin Oncol 26 (Suppl 15): A-4009, 2008.
- Pachman DR, Qin R, Seisler DK, Smith EM, Beutler AS, Ta LE, Lafky JM, Wagner-Johnston ND, Ruddy KJ, Dakhil S, Staff NP, Grothey A, Loprinzi CL. Clinical Course of Oxaliplatin-Induced Neuropathy: Results From the Randomized Phase III Trial N08CB (Alliance). J Clin Oncol. 2015 Oct 20;33(30):3416-22. doi: 10.1200/JCO.2014.58.8533. Epub 2015 Aug 17.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Chemically-Induced Disorders
- Digestive System Diseases
- Nervous System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Poisoning
- Colorectal Neoplasms
- Neurotoxicity Syndromes
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics
- Membrane Transport Modulators
- Anticonvulsants
- Calcium-Regulating Hormones and Agents
- Reproductive Control Agents
- Calcium Channel Blockers
- Tocolytic Agents
- Calcium
- Magnesium Sulfate
Other Study ID Numbers
- NCCTG-N04C7
- CDR0000471238 (Registry Identifier: NCI Physician Data Query)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Colorectal Cancer
-
University of California, San FranciscoCompletedStage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC... and other conditionsUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedRectal Cancer | Colon Cancer | Cancer Survivor | Colorectal Adenocarcinoma | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage I Colorectal Cancer AJCC v8 | Stage II Colorectal Cancer AJCC v8 | Stage... and other conditionsUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedStage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC... and other conditionsUnited States
-
M.D. Anderson Cancer CenterRecruitingColorectal Adenocarcinoma | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage... and other conditionsUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedCancer Survivor | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage I Colorectal Cancer AJCC v8 | Stage II Colorectal Cancer AJCC v8 | Stage IIA Colorectal Cancer AJCC v8 | Stage IIB Colorectal... and other conditionsUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...United States Department of DefenseActive, not recruitingColorectal Adenoma | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage 0 Colorectal Cancer AJCC v8 | Stage I Colorectal Cancer AJCC v8 | Stage II Colorectal Cancer AJCC v8 | Stage IIA Colorectal... and other conditionsUnited States
-
City of Hope Medical CenterRecruitingColorectal Neoplasms | Colorectal Cancer | Colorectal Adenocarcinoma | Colorectal Cancer Stage II | Colorectal Cancer Stage III | Colorectal Cancer Stage IV | Colorectal Neoplasms Malignant | Colorectal Cancer Stage IUnited States, Japan, Italy, Spain
-
University of Roma La SapienzaCompletedColorectal Cancer Stage II | Colorectal Cancer Stage III | Colorectal Cancer Stage IV | Colorectal Cancer Stage 0 | Colorectal Cancer Stage IItaly
-
University of Southern CaliforniaNational Cancer Institute (NCI); AmgenTerminatedStage IV Colorectal Cancer AJCC v7 | Stage IVA Colorectal Cancer AJCC v7 | Stage IVB Colorectal Cancer AJCC v7 | Colorectal Adenocarcinoma | RAS Wild Type | Stage III Colorectal Cancer AJCC v7 | Stage IIIA Colorectal Cancer AJCC v7 | Stage IIIB Colorectal Cancer AJCC v7 | Stage IIIC Colorectal Cancer...United States
Clinical Trials on calcium gluconate
-
University of MalayaUnknown
-
University of East AngliaQuadram Institute BioscienceCompleted
-
University of California, IrvineNot yet recruitingHemorrhage | Trauma | Shock, Hemorrhagic | Hypocalcemia
-
Stanford UniversityCompletedPregnancy Related | Hypocalcemia | Postpartum Hemorrhage | Parturition ComplicationUnited States
-
University of Colorado, DenverNational Center for Advancing Translational Sciences (NCATS)RecruitingOsteoporosisUnited States
-
Michael Patrick AchiamCompleted
-
Rambam Health Care CampusRecruitingElective Cesarean DeliveryIsrael
-
Johns Hopkins UniversityRobert Wood Johnson FoundationCompleted
-
University of Alabama at BirminghamCompleted
-
Bellerophon BCM LLCCompletedCongestive Heart Failure | Acute Myocardial Infarction | ST-Elevation Myocardial InfarctionUnited States, Spain, France, Belgium, Australia, Israel, Canada, Germany, Poland