Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
- Conditions
- Chemotherapeutic Agent ToxicityColorectal CancerNeuropathyNeurotoxicity
- Interventions
- Registration Number
- NCT01099449
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- 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 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 362
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I magnesium sulfate 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). Arm I calcium gluconate 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). Arm I oxaliplatin 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). Arm II placebo Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy). Arm III calcium gluconate 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). Arm III placebo 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). Arm III oxaliplatin 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). Arm II oxaliplatin Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy). Arm III magnesium sulfate 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).
- Primary Outcome Measures
Name Time Method Sensory Area Under the Curve(AUC) Score. Oxaliplatin-induced Sensory Neuropathy as Repeatedly Measured by the EORTC QLQ-CIPN20 Sensory Subscale During Chemotherapy Up to 18 months The oxaliplatin-induced sensory neuropathy as repeatedly measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of Chemotherapy-induced peripheral neuropathy (EORTC QLQ-CIPN20) sensory subscale during the chemotherapy. This is a multivariate repeated measurement of CIPN with possibly variable cycles for every patient. The CIPN sensory subscale will be calculated by standard scoring algorithm and converted to 0-100 scale, where higher scores represent a higher quality of life. Rather than choosing the CIPN20 sensory subscale at a fixed cycle of chemotherapy, we will adopt a summary measure, area under the curve (AUC) of CIPN20 sensory subscale as the primary endpoint. This AUC will be prorated by the number of chemotherapy cycles patients received.
- Secondary Outcome Measures
Name Time Method Time to Onset of Grade 2+ and Grade 3+ Chronic Cumulative Neurotoxicity and the Duration of the Chronic Cumulative Neurotoxicity During and After Chemotherapy Up to 18 months Time to onset of grade 2+ and grade 3+ chronic cumulative neurotoxicity, the duration of the chronic cumulative neurotoxicity during and after the adjuvant oxaliplatin-based chemotherapy. Grades are determined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.0) and oxaliplatin-specific neurotoxicity scale, during and after chemotherapy. Higher grades symbolize greater severity of the adverse event.
Area Under the Curve (AUC) of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of Chemotherapy-induced Peripheral Neuropathy (EORTC QLQ-CIPN20) Motor Neuropathy Subscale Scores Up to 18 Months The oxaliplatin-induced motor neuropathy as repeatedly measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of Chemotherapy-induced peripheral neuropathy (EORTC QLQ-CIPN20) motor neuropathy subscale during the chemotherapy. This is a multivariate repeated measurement of CIPN with possibly variable cycles for every patient. The CIPN motor neuropathy subscale will be calculated by standard scoring algorithm and converted to 0-100 scale, where higher scores represent a higher quality of life. Rather than choosing the CIPN20 motor neuropathy subscale at a fixed cycle of chemotherapy, we will adopt a summary measure, area under the curve (AUC) of CIPN20 motor neuropathy subscale as the endpoint. This AUC will be prorated by the number of chemotherapy cycles patients received.
Area Under the Curve (AUC) of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of Chemotherapy-induced Peripheral Neuropathy (EORTC QLQ-CIPN20) Autonomic Neuropathy Subscale Scores Up to 18 months The oxaliplatin-induced autonomic neuropathy as repeatedly measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire of Chemotherapy-induced peripheral neuropathy (EORTC QLQ-CIPN20) autonomic subscale during the chemotherapy. This is a multivariate repeated measurement of CIPN with possibly variable cycles for every patient. The CIPN autonomic subscale will be calculated by standard scoring algorithm and converted to 0-100 scale, where higher scores represent a higher quality of life. Rather than choosing the CIPN20 autonomic subscale at a fixed cycle of chemotherapy, we will adopt a summary measure, area under the curve (AUC) of CIPN20 autonomic subscale as the endpoint. This AUC will be prorated by the number of chemotherapy cycles patients received.
Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin Up to 18 months This is the percent of patients who scored \>=50 in all sequences of all cycles by arm for side effect Q1: Sensitivity to touching cold. This is a\> repeated measurement of CIPN with possibly variable cycles for every patient. The CIPN subscale will be calculated by standard scoring algorithm and converted to 0-100 scale. Where 0 is no sensitivity and 100 is as bad as it can be.
Incidence of Calcium Gluconate and Magnesium Sulfate-induced Adverse Events as Measured by CTCAE Version 4.0 Up to 18 months Area Under the Curve (AUC) of Patient-reported Quality of Life (QOL) as Measured by the Supplemental QOL Questionnaire Up to 18 months This is a multivariate repeated measurement of CIPN with possibly variable cycles for every patient. The supplemental quality of life (QOL) subscale will be calculated by standard scoring algorithm and converted to 0-100 scale, where higher scores represent a higher quality of life. Rather than choosing the subscale at a fixed cycle of chemotherapy, we will adopt a summary measure, area under the curve (AUC) . This AUC will be prorated by the number of chemotherapy cycles patients received.
Percentage of Patients Experiencing Grade 2+ and Grade 3+ Chronic Cumulative Neurotoxicity. Up to 18 months Grades are determined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE version 4.0) and oxaliplatin-specific neurotoxicity scale, during and after chemotherapy. Higher grades symbolize greater severity of the adverse event.
Cumulative Oxaliplatin Doses That Can be Administered Without Dose-limiting Chronic Neurotoxicity Up to 18 months A patient has a dose-limiting chronic neurotoxicity when they discontinue oxaliplatin-based chemotherapy because of neurotoxicity.
Percentage of Patients Discontinuing Oxaliplatin-based Chemotherapy Because of Neurotoxicity Up to 18 months
Trial Locations
- Locations (401)
Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
🇺🇸Fairbanks, Alaska, United States
Kaiser Permanente - Deer Valley
🇺🇸Antioch, California, United States
North Bay Cancer Center
🇺🇸Fairfield, California, United States
Kaiser Permanente - Fremont
🇺🇸Fremont, California, United States
Kaiser Permanente Fresno Medical Center
🇺🇸Fresno, California, United States
Kaiser Permanente Medical Center - Hayward
🇺🇸Hayward, California, United States
Kaiser Permanente Medical Center - Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente Medical Center - Redwood City
🇺🇸Redwood City, California, United States
Kaiser Permanente Medical Center - Richmond
🇺🇸Richmond, California, United States
Kaiser Permanente Medical Center - Roseville
🇺🇸Roseville, California, United States
Scroll for more (391 remaining)Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital🇺🇸Fairbanks, Alaska, United States