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 - Full Text View

Sponsor:	North Central Cancer Treatment Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00316914

Purpose

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	Intervention	Phase
Colorectal Cancer Neurotoxicity	Drug: calcium gluconate Drug: magnesium sulfate Other: placebo	Phase III

Study Type:	Interventional
Study Design:	Supportive Care, Randomized, Double-Blind, Placebo Control
Official Title:	A Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium to Prevent Oxaliplatin-Induced Sensory Neurotoxicity

Resource links provided by NLM:

MedlinePlus related topics: Calcium Cancer Colorectal Cancer Surgery

Drug Information available for: Magnesium sulfate Oxaliplatin Calcium gluconate Gluconic acid D-Gluconic acid, monosodium salt Manganese gluconate Magnesium

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Percentage of patients with oxaliplatin-induced neurotoxicity as assessed by CTCAE v3.0 [ Designated as safety issue: No ]

Secondary Outcome Measures:

Time to onset of grade 2+ chronic neurotoxicity as assessed by CTCAE v3.0 [ Designated as safety issue: No ]
Time to onset of grade 3+ chronic neurotoxicity as assessed by CTCAE v3.0 [ Designated as safety issue: No ]
Average duration of chronic neuropathic toxicity as assessed by CTCAE v3.0 [ Designated as safety issue: No ]
Percentage of patients discontinuing therapy as assessed by CTCAE v3.0 [ Designated as safety issue: No ]
Average cumulative oxaliplatin dose [ Designated as safety issue: No ]
Average duration of treatment [ Designated as safety issue: No ]
Percentage of patients with acute neuropathic toxicity [ Designated as safety issue: No ]
Incidence of calcium magnesium (CaMg)-induced toxicity [ Designated as safety issue: Yes ]
Percentage of patients experiencing impact on activities of daily living (ADL) [ Designated as safety issue: No ]
Average fatigue from baseline to 1 month [ Designated as safety issue: No ]
Average quality of life from baseline to 1 month
Percentage of patients with grade 2+ chronic neuropathic toxicity who express the GSTP1 1105V polymorphism [ Designated as safety issue: No ]
Time to onset of grade 2+ chronic neuropathic toxicity comparison between patients who either express or don't express the GSTP1 1105V polymorphism [ Designated as safety issue: No ]

Estimated Enrollment:	300
Study Start Date:	January 2006
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Experimental 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.	Drug: calcium gluconate Given IV Drug: magnesium sulfate Given IV
Arm II: 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 Given IV

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the colon or rectum
- Stage II disease
- Stage III disease
- Stage IV disease (completed 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00316914

Locations

United States, Georgia
MBCCOP - Medical College of Georgia Cancer Center
Augusta, Georgia, United States, 30912
United States, Iowa
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, United States, 50309
John Stoddard Cancer Center at Iowa Lutheran Hospital
Des Moines, Iowa, United States, 50316
Mercy Cancer Center at Mercy Medical Center - Des Moines
Des Moines, Iowa, United States, 50314
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
John Stoddard Cancer Center at Iowa Methodist Medical Center
Des Moines, Iowa, United States, 50309
Mercy Capitol Hospital
Des Moines, Iowa, United States, 50307
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
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, United States, 57117-5039
Medical X-Ray Center, PC
Sioux Falls, South Dakota, United States, 57105
Avera Cancer Institute
Sioux Falls, South Dakota, United States, 57105

Sponsors and Collaborators

North Central Cancer Treatment Group

National Cancer Institute (NCI)

Investigators

Investigator:	Charles L. Loprinzi, MD	Mayo Clinic
Investigator:	Daniel Nikcevich, MD, PhD	Duluth Clinic Cancer Center - Duluth
Study Chair:	Axel Grothey, MD	Mayo Clinic
Investigator:	Steven R. Alberts, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Responsible Party:	North Central Cancer Treatment Group ( Charles L. Loprinzi )
Study ID Numbers:	CDR0000471238, NCCTG-N04C7
Study First Received:	April 19, 2006
Last Updated:	July 14, 2009
ClinicalTrials.gov Identifier:	NCT00316914 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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:

Molecular Mechanisms of Pharmacological Action
Neurotoxicity Syndromes
Antineoplastic Agents
Gastrointestinal Diseases
Magnesium Sulfate
Colonic Diseases
Physiological Effects of Drugs
Calcium Channel Blockers
Disorders of Environmental Origin
Anesthetics
Reproductive Control Agents
Rectal Diseases
Membrane Transport Modulators
Oxaliplatin
Neoplasms by Site

Tocolytic Agents
Sensory System Agents
Therapeutic Uses
Anti-Arrhythmia Agents
Analgesics
Digestive System Neoplasms
Nervous System Diseases
Poisoning
Central Nervous System Depressants
Cardiovascular Agents
Intestinal Diseases
Intestinal Neoplasms
Pharmacologic Actions
Neoplasms
Digestive System Diseases

ClinicalTrials.gov processed this record on February 08, 2010