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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2012 by AHS Cancer Control Alberta
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
AHS Cancer Control Alberta
ClinicalTrials.gov Identifier:
NCT01624051
First received: April 26, 2012
Last updated: June 18, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Other: Standard dosing method arm: Cisplatin (chemotherapy) dosing based on body surface area
Other: Experimental dosing method arm: Cisplatin (chemotherapy) dosing based on individual lean body mass
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by AHS Cancer Control Alberta:

Primary Outcome Measures:
  • Dose limiting toxicity rates [ Time Frame: Assessed weekly until patients come off study (an expected average of 9 weeks) ] [ Designated as safety issue: Yes ]
  • Number of Cycles completed [ Time Frame: Assessed weekly until patients come off study (an expected average of 9 weeks) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Survival [ Time Frame: Assessed every 60 days from the date of removal from the trial (an expected average of 9 months) ] [ Designated as safety issue: Yes ]
    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.


Estimated Enrollment: 144
Study Start Date: July 2012
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Body Surface Area Dosing
Standard dosing arm based on body surface area
Other: Standard dosing method arm: Cisplatin (chemotherapy) dosing based on body surface area
Cisplatin dosing calculated at the rate of 75 mg/m2
Experimental: Lean Body Mass Dosing
Experimental dosing arm based on individual lean body mass
Other: Experimental dosing method arm: Cisplatin (chemotherapy) dosing based on individual lean body mass
Cisplatin dosing calculated at the rate of 3.10 mg/kg 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01624051

Contacts
Contact: Michael B Sawyer, MD 780-432-8248 michael.sawyer@albertahealthservices.ca

Locations
Canada, Alberta
Cross Cancer Institute Not yet recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Principal Investigator: Michael B Sawyer, MD         
Sponsors and Collaborators
AHS Cancer Control Alberta
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Michael B Sawyer, MD Medical Oncologist, Cross Cancer Institute
Study Chair: Vickie Baracos, PhD Grant Holder, Department of Oncology, University of Alberta
  More Information

Publications:
Responsible Party: AHS Cancer Control Alberta
ClinicalTrials.gov Identifier: NCT01624051     History of Changes
Other Study ID Numbers: Sawyer - Lung - CCI
Study First Received: April 26, 2012
Last Updated: June 18, 2012
Health Authority: Canada: Health Canada

Keywords provided by AHS Cancer Control Alberta:
cisplatin based chemotherapy
non-small cell lung cancer
lean body mass
sarcopenia

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 27, 2014