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Trial record 5 of 127 for:    colon cancer AND Rectal | ( Map: New Jersey, United States )

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

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ClinicalTrials.gov Identifier: NCT01099449
Recruitment Status : Completed
First Posted : April 7, 2010
Results First Posted : May 23, 2019
Last Update Posted : May 23, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE April 6, 2010
First Posted Date  ICMJE April 7, 2010
Results First Submitted Date  ICMJE January 3, 2017
Results First Posted Date  ICMJE May 23, 2019
Last Update Posted Date May 23, 2019
Study Start Date  ICMJE June 2010
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
Sensory Area Under the Curve(AUC) Score. Oxaliplatin-induced Sensory Neuropathy as Repeatedly Measured by the EORTC QLQ-CIPN20 Sensory Subscale During Chemotherapy [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 6, 2010)
Oxaliplatin-induced sensory neuropathy as repeated measured by the EORTC QLQ-CIPN20 sensory subscale during chemotherapy
Change History Complete list of historical versions of study NCT01099449 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
  • 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 [ Time Frame: 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.
  • 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 [ Time Frame: 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.
  • Percentage of Patients Experiencing Grade 2+ and Grade 3+ Chronic Cumulative Neurotoxicity. [ Time Frame: 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.
  • 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 ]
    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.
  • Cumulative Oxaliplatin Doses That Can be Administered Without Dose-limiting Chronic Neurotoxicity [ Time Frame: 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 [ Time Frame: Up to 18 months ]
  • Percentage of Patients With Acute Neuropathy Associated With Oxaliplatin [ Time Frame: 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 [ Time Frame: Up to 18 months ]
  • Area Under the Curve (AUC) of Patient-reported Quality of Life (QOL) as Measured by the Supplemental QOL Questionnaire [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 6, 2010)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
Official Title  ICMJE 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Supportive Care
Condition  ICMJE
  • Chemotherapeutic Agent Toxicity
  • Colorectal Cancer
  • Neuropathy
  • Neurotoxicity
Intervention  ICMJE
  • Drug: calcium gluconate
    Given IV
  • Drug: magnesium sulfate
    Given IV
  • Other: placebo
    Given IV
  • Drug: oxaliplatin
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: calcium gluconate
    • Drug: magnesium sulfate
    • Drug: oxaliplatin
  • Placebo Comparator: Arm II
    Patients receive placebo IV over 30 minutes immediately before and after oxaliplatin administration (part of FOLFOX chemotherapy).
    Interventions:
    • Other: placebo
    • Drug: oxaliplatin
  • 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).
    Interventions:
    • Drug: calcium gluconate
    • Drug: magnesium sulfate
    • Other: placebo
    • Drug: oxaliplatin
Publications * Loprinzi CL, Qin R, Dakhil SR, Fehrenbacher L, Flynn KA, Atherton P, Seisler D, Qamar R, Lewis GC, Grothey A. Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance). J Clin Oncol. 2014 Apr 1;32(10):997-1005. doi: 10.1200/JCO.2013.52.0536. Epub 2013 Dec 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 4, 2015)
362
Original Estimated Enrollment  ICMJE
 (submitted: April 6, 2010)
354
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States,   Puerto Rico
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01099449
Other Study ID Numbers  ICMJE N08CB
NCCTG-N08CB
CDR0000669660 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2011-02036 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Charles L. Loprinzi, MD Mayo Clinic
PRS Account Alliance for Clinical Trials in Oncology
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP