Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01099449
First received: April 6, 2010
Last updated: June 10, 2012
Last verified: June 2012
  Purpose

RATIONALE: Chemoprotective drugs, such as calcium gluconate and magnesium sulfate, may prevent neurotoxicity caused by oxaliplatin. It is not yet known which administration schedule of calcium gluconate and magnesium sulfate is more effective in preventing neurotoxicity.

PURPOSE: This randomized phase III trial is studying different administration schedules of calcium gluconate and magnesium sulfate and comparing how well they work in neurotoxicity in patients with colon cancer or rectal cancer receiving oxaliplatin-based combination chemotherapy.


Condition Intervention Phase
Chemotherapeutic Agent Toxicity
Colorectal Cancer
Neuropathy
Neurotoxicity
Drug: calcium gluconate
Drug: magnesium sulfate
Other: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Supportive Care
Official Title: A Phase III Randomized, Placebo-Controlled, Double-Blind Study of Intravenous Calcium/Magnesium in Two Different Versions to Prevent Oxaliplatin-Induced Sensory Neurotoxicity

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Oxaliplatin-induced sensory neuropathy as repeatedly measured by the EORTC QLQ-CIPN20 sensory subscale during chemotherapy [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Area under the curve (AUC) of EORTC QLQ-CIPN20 motor subscale and autonomic subscale [ Designated as safety issue: No ]
  • Percentage of patients experiencing grade 2+ and grade 3+ chronic cumulative neurotoxicity (NCI CTCAE version 4.0 and oxaliplatin-specific neurotoxicity scale) during and after chemotherapy [ Designated as safety issue: No ]
  • Time to onset of grade 2+ and grade 3+ chronic cumulative neurotoxicity and the duration of the chronic cumulative neurotoxicity during and after chemotherapy [ Designated as safety issue: No ]
  • Cumulative oxaliplatin doses that can be administered without dose-limiting chronic neurotoxicity and the percentage of patients discontinuing oxaliplatin-based chemotherapy because of neurotoxicity [ Designated as safety issue: No ]
  • Percentage of acute neuropathy associated with oxaliplatin as measured by daily Side Effect Questionnaire during and after oxaliplatin-based chemotherapy (at 1, 3, 6, 12, and 18 months) [ Designated as safety issue: No ]
  • Incidence of calcium gluconate and magnesium sulfate-induced adverse events as measured by CTCAE version 4.0 [ Designated as safety issue: Yes ]
  • AUC of patient-reported quality of life (QOL) as measured by the supplemental QOL questionnaire [ Designated as safety issue: No ]
  • Incidence and expression of GSTP1 or other gene polymorphism with early onset of oxaliplatin-induced neurotoxicity [ Designated as safety issue: No ]

Estimated Enrollment: 354
Study Start Date: June 2010
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).
Drug: calcium gluconate
Given IV
Drug: magnesium sulfate
Given IV
Placebo Comparator: Arm II
Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).
Other: placebo
Given IV
Experimental: Arm III
Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).
Drug: calcium gluconate
Given IV
Drug: magnesium sulfate
Given IV
Other: placebo
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • To determine whether 2 schedules of calcium gluconate and magnesium sulfate infusions (given before and after chemotherapy or just before chemotherapy) can prevent or ameliorate chronic, cumulative oxaliplatin-induced sensory neurotoxicity in patients with colon or rectal cancer receiving adjuvant FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin.

Secondary

  • To determine whether these 2 infusion schedules can increase the cumulative oxaliplatin doses that can be delivered without dose-limiting chronic neurotoxicity.
  • To determine whether these 2 infusion schedules can ameliorate acute neuropathy associated with oxaliplatin.
  • To determine whether these 2 infusion schedules cause adverse events.
  • To investigate whether these 2 infusions schedules influence patient quality of life.
  • To describe baseline and post-treatment neurological quantitative sensory testing abnormalities in the study participants.

Tertiary

  • To explore if polymorphisms in the GSTP1, GSTM1, ERCC2, and XRCC1 genes are associated with early onset of oxaliplatin-induced neurotoxicity.

OUTLINE: This is a multicenter study. Patients are stratified according to age (< 65 years vs ≥ 65 years), gender, regimen (FOLFOX4 vs modified FOLFOX6 vs other), and stage of disease (II vs III vs IV). Patients are randomized to 1 of 3 treatment arms.

  • Arm I: Patients receive calcium gluconate IV and magnesium sulfate IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy comprising leucovorin calcium, fluorouracil, and oxaliplatin).
  • Arm II: Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).
  • Arm III: Patients receive calcium gluconate and magnesium sulfate IV over 30 minutes immediately before and placebo IV over 30 minutes immediately after oxaliplatin administration (part of FOLFOX chemotherapy).

In all arms, courses repeat every 14 days for 6 months in the absence of disease progression or unacceptable toxicity.

Blood samples are collected before the second course of treatment for translational research.

Patients complete questionnaires on side effects, quality of life, and chemotherapy-induced peripheral neuropathy periodically.

After completion of study treatment, patients are followed up at 3, 6, 12, and 18 months.

  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
  • Has undergone curative resection and is considered to have stage II or III disease or completely resected stage IV disease with no evidence of residual tumor
  • Scheduled to receive 6 months of oxaliplatin-based adjuvant chemotherapy with 85 mg/m^2 oxaliplatin every 2 weeks (this includes, for instance, FOLFOX4 or modified FOLFOX6)

    • Patients receiving bevacizumab or cetuximab in combination with FOLFOX as part of a clinical trial or clinical practice are eligible

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • WBC ≥ 3,000/mm^3
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10.0 g/dL
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Serum creatinine ≤ 1.5 times ULN
  • Serum calcium ≤ 1.2 times ULN
  • Serum magnesium ≤ 1.2 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Able to complete questionnaires (alone or with assistance)
  • Able to comply with study treatment
  • Willing to return to enrolling institution for follow-up
  • Willing to provide blood sample for research purposes
  • No pre-existing peripheral neuropathy of any grade
  • No family history of a genetic/familial neuropathy
  • No second or third degree AV heart block or a history of second or third degree heart block

    • Bundle branch blocks are allowed.
  • No other medical conditions that, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Central venous access line present, or scheduled to have a central line placed before starting chemotherapy and study treatment
  • No prior treatment with neurotoxic chemotherapy (e.g., oxaliplatin, cisplatin, taxanes, or vinca alkaloids)
  • No concurrent digitalis medication
  • No concurrent treatment with the anticonvulsants carbamazepine (e.g., Tegretol®), phenytoin (e.g., Dilantin®), valproic acid (e.g., Depakene®), gabapentin (Neurontin®), or pregabalin (Lyrica®)
  • No concurrent neurotropic agents, including venlafaxine (Effexor), desvenlafaxine (Pristiq®), milnacipran (Savella®), or duloxetine (Cymbalta)
  • No concurrent tricyclic antidepressants (such as amitryptilline), or any other agent specifically being given to prevent or treat neuropathy
  • No concurrent drugs given as a neuroprotectant
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01099449

  Show 405 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Charles L. Loprinzi, MD North Central Cancer Treatment Group
  More Information

Additional Information:
No publications provided

Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT01099449     History of Changes
Other Study ID Numbers: CDR0000669660, NCCTG-N08CB
Study First Received: April 6, 2010
Last Updated: June 10, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
neurotoxicity
neuropathy
chemotherapeutic agent toxicity
stage II colon cancer
stage III colon cancer
stage IV colon cancer
stage II rectal cancer
stage III rectal cancer
stage IV rectal cancer
adenocarcinoma of the colon
adenocarcinoma of the rectum

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Neurotoxicity Syndromes
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Nervous System Diseases
Poisoning
Substance-Related Disorders
Calcium, Dietary
Magnesium Sulfate
Oxaliplatin
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Anesthetics
Central Nervous System Depressants

ClinicalTrials.gov processed this record on April 17, 2014