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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary:

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.


Detailed Summary:

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
Sponsor: Alliance for Clinical Trials in Oncology

Current Primary Outcome: Oxaliplatin-induced sensory neuropathy as repeatedly measured by the EORTC QLQ-CIPN20 sensory subscale during chemotherapy [ Time Frame: Up to 18 months ]

Original Primary Outcome: Oxaliplatin-induced sensory neuropathy as repeated measured by the EORTC QLQ-CIPN20 sensory subscale during chemotherapy

Current Secondary Outcome:

  • Area under the curve (AUC) of EORTC QLQ-CIPN20 motor subscale and autonomic subscale [ Time Frame: Up to 18 months ]
  • 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 [ Time Frame: Up to 18 months ]
  • Time to onset of grade 2+ and grade 3+ chronic cumulative neurotoxicity and the duration of the chronic cumulative neurotoxicity during and after chemotherapy [ Time Frame: Up to 18 months ]
  • Cumulative oxaliplatin doses that can be administered without dose-limiting chronic neurotoxicity and the percentage of patients discontinuing oxaliplatin-based chemotherapy because of neurotoxicity [ Time Frame: Up to 18 months ]
  • 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) [ Time Frame: Up to 18 months ]
  • Incidence of calcium gluconate and magnesium sulfate-induced adverse events as measured by CTCAE version 4.0 [ Time Frame: Up to 18 months ]
  • AUC of patient-reported quality of life (QOL) as measured by the supplemental QOL questionnaire [ Time Frame: Up to 18 months ]
  • Incidence and expression of GSTP1 or other gene polymorphism with early onset of oxaliplatin-induced neurotoxicity [ Time Frame: Up to 18 months ]


Original Secondary Outcome:

  • Area under the curve (AUC) of EORTC QLQ-CIPN20 motor subscale and autonomic subscale
  • Percentage of patients experiencing grade 2+ and grade 3+ chronic cumulative neurotoxicity (NCI CTCAE active version and oxaliplatin-specific neurotoxicity scale) during and after chemotherapy
  • Time to onset of grade 2+ and grade 3+ chronic cumulative neurotoxicity and the duration of the chronic cumulative neurotoxicity during and after chemotherapy
  • Cumulative oxaliplatin doses that can be administered without dose-limiting chronic neurotoxicity and the percentage of patients discontinuing oxaliplatin-based chemotherapy because of neurotoxicity
  • 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)
  • Incidence of calcium gluconate and magnesium sulfate-induced adverse events as measured by CTCAE active version
  • AUC of patient-reported quality of life (QOL) as measured by the supplemental QOL questionnaire
  • Incidence and expression of GSTP1 or other gene polymorphism with early onset of oxaliplatin-induced neurotoxicity


Information By: Alliance for Clinical Trials in Oncology

Dates:
Date Received: April 6, 2010
Date Started: June 2010
Date Completion:
Last Updated: August 11, 2016
Last Verified: August 2016