Phase 3
N=353
Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
Chemotherapeutic Agent Toxicity · Colorectal Cancer · Neuropathy · Neurotoxicity
Bottom Line
View on ClinicalTrials.gov: NCT01099449 ↗Enrolled (actual)
353
Serious AEs
8.5%
Results posted
May 2019
Primary outcome: Primary: Sensory Area Under the Curve(AUC) Score. Oxaliplatin-induced Sensory Neuropathy as Repeatedly Measured by the EORTC QLQ-CIPN20 Sensory Subscale During Chemotherapy — 89.2; 88.3; 87.1 score on a scale — p=.73
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- calcium gluconate (Drug); magnesium sulfate (Drug); placebo (Other); oxaliplatin (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Alliance for Clinical Trials in Oncology
- Primary completion
- Dec 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Sensory Area Under the Curve(AUC) Score. Oxaliplatin-induced Sensory Neuropathy as Repeatedly Measured by the EORTC QLQ-CIPN20 Sensory Subscale During Chemotherapy |
89.2; 88.3; 87.1 | .73 |
| SECONDARY 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 |
89.8; 86.7; 84.5 | .054 |
| SECONDARY 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 |
94.1; 93.3; 91.6 | .29 |
| SECONDARY Percentage of Patients Experiencing Grade 2+ and Grade 3+ Chronic Cumulative Neurotoxicity. |
42.7; 44.8; 46.1; 7.7; 7.8; 7.8 | — |
| SECONDARY Time to Onset of Grade 2+ and Grade 3+ Chronic Cumulative Neurotoxicity and the Duration of the Chronic Cumulative Neurotoxicity During and After Chemotherapy |
171; 173; 171; NA; 208; NA | — |
| SECONDARY Cumulative Oxaliplatin Doses That Can be Administered Without Dose-limiting Chronic Neurotoxicity |
8.1; 8.4; 8.0 | .89 |
| SECONDARY Percentage of Patients Discontinuing Oxaliplatin-based Chemotherapy Because of Neurotoxicity |
34.7; 27.7; 30.5 | .52 |
| SECONDARY Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin |
10; 13; 14; 24; 27; 28 | — |
| SECONDARY Incidence of Calcium Gluconate and Magnesium Sulfate-induced Adverse Events as Measured by CTCAE Version 4.0 |
290; 259; 296 | — |
| SECONDARY Area Under the Curve (AUC) of Patient-reported Quality of Life (QOL) as Measured by the Supplemental QOL Questionnaire |
86.7; 86.2; 84.5; 90.1; 88.8; 88.0 | — |
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.
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT01099449). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.