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

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 3

Conditions: Neurotoxicity; Colorectal Cancer

Treatments: Other: placebo; Drug: calcium gluconate; Drug: magnesium sulfate

Study type: Interventional

Funder types: Other; NETWORK; NIH

Identifiers

NCT00316914

CDR0000471238 (Registry Identifier)

NCCTG-N04C7

Details and patient eligibility

About

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.

Full 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.

Enrollment: 104 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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104 participants in 2 patient groups, including a placebo group

Ca/Mg

Experimental group

Description:

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.

Treatment:

Drug: magnesium sulfate

Drug: calcium gluconate

Placebo

Placebo Comparator group

Description:

Patients receive a placebo IV over 30 minutes immediately before and after each oxaliplatin administration (once every 2 weeks) of their assigned chemotherapy regimen.

Treatment:

Other: placebo