NCT00316914

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
104

participants targeted

Target at below P25 for phase_3 colorectal-cancer

Timeline
Completed

Started Jan 2006

Typical duration for phase_3 colorectal-cancer

Geographic Reach
1 country

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2006

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

April 19, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 21, 2006

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2008

Completed
4.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2012

Completed
5 months until next milestone

Results Posted

Study results publicly available

March 25, 2013

Completed
Last Updated

August 11, 2016

Status Verified

July 1, 2016

Enrollment Period

2 years

First QC Date

April 19, 2006

Results QC Date

November 26, 2012

Last Update Submit

July 11, 2016

Conditions

Colorectal CancerNeurotoxicity

Keywords

neurotoxicitystage II colon cancerstage III colon canceradenocarcinoma of the colonstage II rectal cancerstage III rectal cancerstage IV rectal cancerstage IV colon canceradenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (1)

  • Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event

    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 Outcomes (11)

  • 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

  • +6 more secondary outcomes

Study Arms (2)

Ca/Mg

EXPERIMENTAL

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 gluconateDrug: magnesium sulfate

Placebo

PLACEBO COMPARATOR

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

Interventions

calcium gluconateDRUG

Given IV

Ca/Mg
magnesium sulfateDRUG

Given IV

Ca/Mg
placeboOTHER

Given IV

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (14)

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, 30912, United States

Location

Mercy Capitol Hospital

Des Moines, Iowa, 50307, United States

Location

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, 50309, United States

Location

John Stoddard Cancer Center at Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at John Stoddard Cancer Center

Des Moines, Iowa, 50309, United States

Location

Medical Oncology and Hematology Associates at Mercy Cancer Center

Des Moines, Iowa, 50314, United States

Location

Mercy Cancer Center at Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

Location

John Stoddard Cancer Center at Iowa Lutheran Hospital

Des Moines, Iowa, 50316, United States

Location

Bismarck Cancer Center

Bismarck, North Dakota, 58501, United States

Location

Medcenter One Hospital Cancer Care Center

Bismarck, North Dakota, 58501, United States

Location

Mid Dakota Clinic, PC

Bismarck, North Dakota, 58501, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Medical X-Ray Center, PC

Sioux Falls, South Dakota, 57105, United States

Location

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, 57117-5039, United States

Location

Related Publications (3)

  • 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.

    PMID: 21189381RESULT

  • 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.

    RESULT

  • 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.

    PMID: 26282635DERIVED

MeSH Terms

Conditions

Colorectal NeoplasmsNeurotoxicity SyndromesColonic NeoplasmsRectal Neoplasms

Interventions

Calcium GluconateMagnesium Sulfate

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesNervous System DiseasesPoisoningChemically-Induced Disorders

Intervention Hierarchy (Ancestors)

GluconatesSugar AcidsAcids, AcyclicCarboxylic AcidsOrganic ChemicalsHydroxy AcidsCarbohydratesMagnesium CompoundsInorganic ChemicalsSulfatesSulfuric AcidsSulfur AcidsSulfur Compounds

Limitations and Caveats

Data cutoff was done after 127 days because of premature study closure and because of the protocol modification mandating that the Ca/Mg therapy be discontinued.

Results Point of Contact

Title
Dr. Axel Grothey
Organization
Mayo Clinic
grothey.axel@mayo.edu
507-184-2779

Study Officials

  • Axel Grothey, MD

    Mayo Clinic

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
SUPPORTIVE CARE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 19, 2006

First Posted

April 21, 2006

Study Start

January 1, 2006

Primary Completion

January 1, 2008

Study Completion

November 1, 2012

Last Updated

August 11, 2016

Results First Posted

March 25, 2013

Record last verified: 2016-07

Locations

US(14)