Oxaliplatin Pharmacokinetics With and Without Ca2+/MG2+ Infusion in Colorectal Cancer Patients

The investigators hypothesize that Ca2+/MG2+ infusions will not have a significant effect on oxaliplatin pharmacokinetics.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Colorectal Carcinoma; Neoplasms, Colorectal
• Intervention / Treatment: Other: (supplement) Calcium and Magnesium

Detailed Description

This is a clinical pharmacology prospective non-randomized trial to determine oxaliplatin pharmacokinetics in the presence and absence of calcium and magnesium supplementation.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Michael Sawyer, MD; Phone Number: 780-432-8248; Email: Michael.Sawyer@albertahealthservices.ca

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
      • Sub-Investigator: Judith Meza-Junco, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must have Metastatic Colorectal Cancer (stage IV)
• Patients who were treated with 5FU and leucovorin in the adjuvant setting or with 5FU and leucovorin (LV)or/and FOLFIRI regimen for metastatic setting may be eligible for this trial.
• Patients must be ≥ 18 years
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Patients must have adequate renal function of creatinine < 1.5mg/dl and a creatinine clearance > 45ml/min. Patients must have adequate hepatic function with a bilirubin > 1.5 mg/dl and AST (normal range 0-14/L) and ALT (normal range 0-49 U/L) in the absence of liver metastasis or </= 5X the upper limit of normal of AST and ALT in the presence of liver metastasis.
• Patients must have adequate bone marrow function with absolute neutrophil count(ANC)≥ 1,500/цl and platelets ≥ 100,000/цl and a hemoglobin ≥ 10g/d.
• Patients must be willing and able to comply with the study protocol for the study duration and patients must give written informed consent prior to any study-specific screening procedures with the understanding that the patient may withdraw consent at any time without prejudice.
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Also,women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. The investigator is requested to advise the patient how to achieve an adequate contraception.
• Life expectancy longer that 6 months

Exclusion Criteria:

• Patients who have received oxaliplatin previously
• Patients with known peripheral neuropathy ≥ grade 2 according to the WHO scale
• Patients who have tested positive for HIV
• Patients with other significant medical, psychiatric disorders tha, in the opinion of the investigator, will exclude the patient from the study for compliance of safety reasons.
• Patients who cannot swallow
• History of known allergy to oxaliplatin or other platinum compounds,to 5-FU, to LV, or to any ingredients in the formulations or the containers
• Participation in another clinical trial with any investigational drug within 30 days prior to study screening
• Pernicious anemia or other megaloblastic anemia with vitamin B12 deficiency
• Patient with concomitant treatment with drugs/ingredients reported to have a potential activity to prevent peripheral sensory neuropathy (PSN)
• Patients who haven't successfully completed local therapy for previously treated CNS metastases & who haven't been discontinued with corticosteroid for >4kws before starting chemotherapy. Patients with asymptomatic brain mets who have no evidence of midline shift on CT/MRI may be enrolled without initiation of local therapy for the CNS mets. Repeat scan must be performed < 4wks to ensure no progression.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ca2+/Mg2+ pre & post cycle 1; Arm A:Ca2+/Mg2+: Ca++gluconate 1gr & Mg++sulfate 1g given IV pre & post cycle 1	Other: (supplement) Calcium and Magnesium; FOLFOX 6: Oxaliplatin (Eloxatin®): 100mg/m2 x 2hrs IV with 250ml of dextrose 5%; leucovorin 200mg/m2 with oxaliplatin; then IV bolus of 5FU 400mg/m2 and 5FU 2400mg/m2 in a 46 hr continuous IV. Each cycle is 14 days, approximately 8-12 cycles planned. XELOX: Oxaliplatin 130mg/m2 x 2hrs IV in 250ml of dextrose 5% on day 1; plus oral capecitabine 1000mg/m2 bid on days 1-15 3 wk cycles. Ca2+/Mg2: Ca++gluconate 1gr & Mg++sulfate 1g given IV pre & post cycle 1 (Arm A) or cycle 2 (Arm B); Other Names: oxaliplatin= eloxatin, Capecitabine=Xeloda
Active Comparator: Ca2+/Mg2+pre & post cycle 2; Arm B:Ca2+/Mg2+: Ca++gluconate 1gr & Mg++sulfate 1g given IV pre & post cycle 2	Other: (supplement) Calcium and Magnesium; FOLFOX 6: Oxaliplatin (Eloxatin®): 100mg/m2 x 2hrs IV with 250ml of dextrose 5%; leucovorin 200mg/m2 with oxaliplatin; then IV bolus of 5FU 400mg/m2 and 5FU 2400mg/m2 in a 46 hr continuous IV. Each cycle is 14 days, approximately 8-12 cycles planned. XELOX: Oxaliplatin 130mg/m2 x 2hrs IV in 250ml of dextrose 5% on day 1; plus oral capecitabine 1000mg/m2 bid on days 1-15 3 wk cycles. Ca2+/Mg2: Ca++gluconate 1gr & Mg++sulfate 1g given IV pre & post cycle 1 (Arm A) or cycle 2 (Arm B); Other Names: oxaliplatin= eloxatin, Capecitabine=Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary objective of this study is to determine potential pharmacokinetic interactions between oxaliplatin and calcium and magnesium.	Post cycle 2 and 3

Collaborators and Investigators

• Sponsor: AHS Cancer Control Alberta
• Investigators: Study Chair: Michael Sawyer, MD, Alberta Health Services

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): September 1, 2015
• Study Completion (Anticipated): September 1, 2015

Study Registration Dates

• First Submitted: July 2, 2010
• First Submitted That Met QC Criteria: July 2, 2010
• First Posted (Estimate): July 5, 2010

Study Record Updates

• Last Update Posted (Estimate): October 1, 2014
• Last Update Submitted That Met QC Criteria: September 29, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: adverse effects; magnesium; calcium; kinetics, drug
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Calcium-Regulating Hormones and Agents; Capecitabine; Oxaliplatin; Calcium
• Other Study ID Numbers: 25408