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:
North Central Cancer Treatment Group
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
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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:
Drug Information available for:
Calcium Gluconate
Sodium gluconate
Manganese gluconate
Magnesium
Magnesium sulfate
Sulfate ion
Oxaliplatin
U.S. FDA Resources
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
Show 405 Study LocationsSponsors 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 May 21, 2013