Clinical trial NCT01099449
Conditions: Chemotherapeutic Agent Toxicity Colorectal Cancer Neuropathy Neurotoxicity
Keywords: 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
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2010-06-01; Completion date: 2013-03-01
Enrollment: 362 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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 2: Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy). arm 3: 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).
Interventions: intervention 1: calcium gluconate intervention 2: magnesium sulfate intervention 3: placebo intervention 4: oxaliplatin
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: None

Protocol documents: