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A Study Comparing Chemotherapy Dosing Based on Either Standard Body Surface Area or Lean Body Mass in Patients With Advanced Lung Cancer

Primary Purpose

Lung Cancer

Status
Unknown status
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Standard dosing method arm: Cisplatin (chemotherapy) dosing based on body surface area
Experimental dosing method arm: Cisplatin (chemotherapy) dosing based on individual lean body mass
Sponsored by
AHS Cancer Control Alberta
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring cisplatin based chemotherapy, non-small cell lung cancer, lean body mass, sarcopenia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Recommendation from treating oncologist to receive a cisplatin based chemotherapy regimen, specifically either cisplatin/vinorelbine or cisplatin/gemcitabine
  • > or = 18 years of age
  • Histologically proven diagnosis of non-small cell lung cancer, Stage IIIB or IV
  • Adequate renal function: creatinine < 1.5 mg/dL or < 132 µmol/L and creatinine clearance of > 45 mL/min using the Cockcroft-Gault formula
  • Adequate hepatic function: bilirubin < 1.5 mg/dL or < 25 µmol/L and AST and ALT < 2 times upper limit of normal, unless there is evidence of liver metastases, in which case < 5 times upper limit of normal
  • Adequate hematological function: absolute neutrophil count (ANC) > 1.5 x 109/L and platelets > 100 x 109/L and hemoglobin > 100 g/L
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
  • Negative serum pregnancy test for women of childbearing potential. Women and men of child bearing potential must use effective contraception defined as the simultaneous use of two reliable methods unless abstinence is the chosen method.
  • Life expectancy of > 4 months in the opinion of the treating oncologist
  • Prior radiotherapy is allowed (unless > 25% of bone marrow stores) if this radiation was > 4 weeks before study entry and patient has fully recovered from toxicity of this treatment
  • Willingness to comply with the study protocol
  • Ability to give written informed consent with the understanding that it may be withdrawn at any time without prejudice

Exclusion Criteria:

  • Pregnant or lactating women
  • Brain metastases (a CT or MRI is not required to rule out brain metastases unless there is clinical suspicion)
  • Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix, in situ ductal breast cancer, non-melanoma skin cancer or low grade bladder cancer
  • Patients who have had major surgery within three weeks of enrollment without a full recovery
  • Prior treatment with any anticancer therapy
  • Patients who have tested positive for HIV
  • Any significant medical or psychiatric condition that, in the opinion of the investigator, will exclude the patient from the study for compliance or safety reasons

Sites / Locations

  • Cross Cancer InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Body Surface Area Dosing

Lean Body Mass Dosing

Arm Description

Standard dosing arm based on body surface area

Experimental dosing arm based on individual lean body mass

Outcomes

Primary Outcome Measures

Dose limiting toxicity rates
Number of Cycles completed

Secondary Outcome Measures

Survival
If a patient has deceased, the date of death is recorded. If a patient is alive, the status is checked again in another 60 days. This is carried out through health records and not through direct contact with the patient.

Full Information

First Posted
April 26, 2012
Last Updated
September 26, 2014
Sponsor
AHS Cancer Control Alberta
Collaborators
Canadian Institutes of Health Research (CIHR)
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1. Study Identification

Unique Protocol Identification Number
NCT01624051
Brief Title
A Study Comparing Chemotherapy Dosing Based on Either Standard Body Surface Area or Lean Body Mass in Patients With Advanced Lung Cancer
Official Title
A Phase II Double Blind Randomized Trial Comparing Standard Dosing Based on Body Surface Area Versus Dosing Based on Personalized Lean Body Mass in Patients With Stage IIIB or IV Non-Small Cell Lung Cancer Receiving First Line Cisplatin Based Chemotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
September 2014
Overall Recruitment Status
Unknown status
Study Start Date
July 2014 (undefined)
Primary Completion Date
September 2015 (Anticipated)
Study Completion Date
September 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AHS Cancer Control Alberta
Collaborators
Canadian Institutes of Health Research (CIHR)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Cancer patients are highly variable in their body composition, specifically in the proportion of fat and muscle. Some patients tend to gain fat and lose muscle (or lean body mass) at the same time. These patients can develop severe muscle wasting, termed sarcopenia. Patients with sarcopenia have more severe treatment related toxicity requiring delays, dose reductions and stopping of treatment, and have reduced survival. One potential explanation for this is that patients with sarcopenia have a reduced volume of lean body mass into which chemotherapy drugs are distributed, resulting in a higher concentration and greater toxicity. This study will randomize lung cancer patients to either the standard dosing strategy based on body surface area or experimental, personalized dosing based on lean body mass. Based on retrospective findings in this patient population, the investigators expect to find that severe toxicity will be reduced for sarcopenic patients on the personalized dosing arm based on lean body mass.
Detailed Description
Retrospective findings of NSCLC patients treated with a cisplatin based chemotherapy regimen show that although all were given cisplatin at the standard rate of 75 mg/m2 according to lean body mass, when this was expressed in relation to individual lean body mass, there was a high degree of variation. Incidence of dose limiting toxicity was 41% in patients whose dose was within + 25% of the median value. However, sarcopenic patients received on average a 35% higher dose and 80% of these patients experienced severe toxicity requiring dose reduction or termination of therapy, a clinically unacceptable level. The relatively muscular subset of patients with higher lean body mass had a reduced level of severe toxicity compared to those at the median dose. These findings have led to the design of a study with the goal of reducing high levels of toxicity in sarcopenic patients. If the expected level of dose limiting toxicity in sarcopenic patients is 80% based on the standard method of dosing, this could be expected to be reduced to the median value of 41% dose limiting toxicity by the administration of cisplatin scaled to individual lean body mass. Hypothesis: Levels of severe toxicity in sarcopenic patients may be reduced to clinically acceptable levels by cisplatin dosing scaled to 3.1 mg/kg lean body mass compared with standard dosing of 75 mg/m2 based on body surface area.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Cancer
Keywords
cisplatin based chemotherapy, non-small cell lung cancer, lean body mass, sarcopenia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
144 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Body Surface Area Dosing
Arm Type
Active Comparator
Arm Description
Standard dosing arm based on body surface area
Arm Title
Lean Body Mass Dosing
Arm Type
Experimental
Arm Description
Experimental dosing arm based on individual lean body mass
Intervention Type
Other
Intervention Name(s)
Standard dosing method arm: Cisplatin (chemotherapy) dosing based on body surface area
Intervention Description
Cisplatin dosing calculated at the rate of 75 mg/m2
Intervention Type
Other
Intervention Name(s)
Experimental dosing method arm: Cisplatin (chemotherapy) dosing based on individual lean body mass
Intervention Description
Cisplatin dosing calculated at the rate of 3.10 mg/kg lean body mass
Primary Outcome Measure Information:
Title
Dose limiting toxicity rates
Time Frame
Assessed weekly until patients come off study (an expected average of 9 weeks)
Title
Number of Cycles completed
Time Frame
Assessed weekly until patients come off study (an expected average of 9 weeks)
Secondary Outcome Measure Information:
Title
Survival
Description
If a patient has deceased, the date of death is recorded. If a patient is alive, the status is checked again in another 60 days. This is carried out through health records and not through direct contact with the patient.
Time Frame
Assessed every 60 days from the date of removal from the trial (an expected average of 9 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Recommendation from treating oncologist to receive a cisplatin based chemotherapy regimen, specifically either cisplatin/vinorelbine or cisplatin/gemcitabine > or = 18 years of age Histologically proven diagnosis of non-small cell lung cancer, Stage IIIB or IV Adequate renal function: creatinine < 1.5 mg/dL or < 132 µmol/L and creatinine clearance of > 45 mL/min using the Cockcroft-Gault formula Adequate hepatic function: bilirubin < 1.5 mg/dL or < 25 µmol/L and AST and ALT < 2 times upper limit of normal, unless there is evidence of liver metastases, in which case < 5 times upper limit of normal Adequate hematological function: absolute neutrophil count (ANC) > 1.5 x 109/L and platelets > 100 x 109/L and hemoglobin > 100 g/L Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 Negative serum pregnancy test for women of childbearing potential. Women and men of child bearing potential must use effective contraception defined as the simultaneous use of two reliable methods unless abstinence is the chosen method. Life expectancy of > 4 months in the opinion of the treating oncologist Prior radiotherapy is allowed (unless > 25% of bone marrow stores) if this radiation was > 4 weeks before study entry and patient has fully recovered from toxicity of this treatment Willingness to comply with the study protocol Ability to give written informed consent with the understanding that it may be withdrawn at any time without prejudice Exclusion Criteria: Pregnant or lactating women Brain metastases (a CT or MRI is not required to rule out brain metastases unless there is clinical suspicion) Previous or concurrent malignancies, excluding curatively treated in situ carcinoma of the cervix, in situ ductal breast cancer, non-melanoma skin cancer or low grade bladder cancer Patients who have had major surgery within three weeks of enrollment without a full recovery Prior treatment with any anticancer therapy Patients who have tested positive for HIV Any significant medical or psychiatric condition that, in the opinion of the investigator, will exclude the patient from the study for compliance or safety reasons
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michael B Sawyer, MD
Phone
780-432-8248
Email
michael.sawyer@albertahealthservices.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael B Sawyer, MD
Organizational Affiliation
Medical Oncologist, Cross Cancer Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Vickie Baracos, PhD
Organizational Affiliation
Grant Holder, Department of Oncology, University of Alberta
Official's Role
Study Chair
Facility Information:
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael B Sawyer, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
18539529
Citation
Prado CM, Lieffers JR, McCargar LJ, Reiman T, Sawyer MB, Martin L, Baracos VE. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008 Jul;9(7):629-35. doi: 10.1016/S1470-2045(08)70153-0. Epub 2008 Jun 6.
Results Reference
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PubMed Identifier
19887488
Citation
Tan BH, Birdsell LA, Martin L, Baracos VE, Fearon KC. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin Cancer Res. 2009 Nov 15;15(22):6973-9. doi: 10.1158/1078-0432.CCR-09-1525. Epub 2009 Nov 3.
Results Reference
background
PubMed Identifier
17545532
Citation
Prado CM, Baracos VE, McCargar LJ, Mourtzakis M, Mulder KE, Reiman T, Butts CA, Scarfe AG, Sawyer MB. Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity. Clin Cancer Res. 2007 Jun 1;13(11):3264-8. doi: 10.1158/1078-0432.CCR-06-3067.
Results Reference
background
PubMed Identifier
19351764
Citation
Prado CM, Baracos VE, McCargar LJ, Reiman T, Mourtzakis M, Tonkin K, Mackey JR, Koski S, Pituskin E, Sawyer MB. Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment. Clin Cancer Res. 2009 Apr 15;15(8):2920-6. doi: 10.1158/1078-0432.CCR-08-2242. Epub 2009 Apr 7.
Results Reference
background
PubMed Identifier
20085939
Citation
Antoun S, Birdsell L, Sawyer MB, Venner P, Escudier B, Baracos VE. Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study. J Clin Oncol. 2010 Feb 20;28(6):1054-60. doi: 10.1200/JCO.2009.24.9730. Epub 2010 Jan 19.
Results Reference
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A Study Comparing Chemotherapy Dosing Based on Either Standard Body Surface Area or Lean Body Mass in Patients With Advanced Lung Cancer

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