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

This study has been completed.
Sponsor:
Collaborators:
North Central Cancer Treatment Group
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00316914
First received: April 19, 2006
Last updated: February 19, 2013
Last verified: February 2013

April 19, 2006
February 19, 2013
January 2006
January 2008   (final data collection date for primary outcome measure)
Percentage of Patients With Oxaliplatin-induced Grade 2+ Chronic Neuropathic Adverse Event [ Time Frame: 127 days ] [ Designated as safety issue: Yes ]
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)
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Complete list of historical versions of study NCT00316914 on ClinicalTrials.gov Archive Site
  • Time to Onset of Grade 2+ Chronic Neurotoxicity [ Time Frame: 127 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    Neurotoxicity was assessed by CTCAE v3.0.
  • Average Duration of Chronic Neuropathic Toxicity [ Time Frame: 127 days ] [ Designated as safety issue: No ]
    Neuropathic adverse events were assessed by CTCAE v3.0.
  • Percentage of Patients Discontinuing Therapy for Chronic Neurotoxicity [ Time Frame: 127 days ] [ Designated as safety issue: No ]
    Neurotoxicity were assessed by CTCAE v3.0.
  • Average Cumulative Oxaliplatin Dose [ Time Frame: 127 days ] [ Designated as safety issue: No ]
  • Average Duration of Oxaliplatin-containing Treatment [ Time Frame: 127 days ] [ Designated as safety issue: No ]
  • Percentage of Patients With Acute Neuropathic Adverse Event [ Time Frame: 127 days ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Adverse Events were measured using CTCAE V3.0.
  • Percentage of Patients Experiencing Impact on Activities of Daily Living (ADL) [ Time Frame: 127 days ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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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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.

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Supportive Care
  • Colorectal Cancer
  • Neurotoxicity
  • Drug: calcium gluconate
    Given IV
  • Drug: magnesium sulfate
    Given IV
  • Other: placebo
    Given IV
  • 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.
    Interventions:
    • Drug: calcium gluconate
    • Drug: magnesium sulfate
  • 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.
    Intervention: Other: placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
104
November 2012
January 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00316914
CDR0000471238, NCCTG-N04C7
Yes
Alliance for Clinical Trials in Oncology
Alliance for Clinical Trials in Oncology
  • National Cancer Institute (NCI)
  • North Central Cancer Treatment Group
Principal Investigator: Charles L. Loprinzi, MD Mayo Clinic
Principal Investigator: Daniel Nikcevich, MD, PhD Duluth Clinic Cancer Center - Duluth
Study Chair: Axel Grothey, MD Mayo Clinic
Principal Investigator: Steven R. Alberts, MD Mayo Clinic
Alliance for Clinical Trials in Oncology
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP