Impact of Fat-free Mass in the Carboplatin Calculated Dose and Chemotherapeutic Toxicity in Patients With Advanced NSCLC

Lung Cancer Clinical Trial

Official title:

Impact of Fat-free Mass in the Carboplatin Calculated Dose and Chemotherapeutic Toxicity in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02734069
• Other study ID #: INCAN/TOX/CBP
• Status: Recruiting
• Start date: February 2016
• Est. completion date: December 2025

Study information

• Verified date: January 2024
• Source: Instituto Nacional de Cancerologia de Mexico
• Contact: Oscar Arrieta, MD, M Sc
• Phone: 015556280400
• Email: ogar[@]unam.mx
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study evaluate the association of body composition (mainly free-fat mass), clinical and biochemical parameters with development of toxicity in patients under treatment with Carboplatin/Paclitaxel in advanced NSCLC.

Description:

BACKGROUND

Lung cancer (LC) is the leading cause of cancer deaths worldwide, are attributed about 13% of all new cases of cancer and accounts for 19.4% of deaths from malignancies. In Mexico, this cancer is also the leading cause of death in malignant neoplasias. One of the reasons attributable the high mortality from this disease is that most cases are detected in advanced stages and this depends prognosis and treatment. Within the classification of LC the most prevalent is the Non Small Cell Lung Cancer (NSCLC); for which the considered first-line standard treatment is palliative cytotoxic chemotherapy, as the combination of carboplatin with paclitaxel and in the other hand one of the most recent combinations Carboplatin with Pemetrexed.

Malnutrition may affect 80% of patients with advanced cancer and is associated with up to 20% of deaths, with an increased risk in the development of complications and mortality and can extend the hospital stay up to 90%, increasing the cost of treatment in a 35-75%. Similarly, in a previous study at INCan, the degree of malnutrition in patients with LC was associated with cytotoxic chemotherapy toxicity and poorer prognosis and poorer quality of life. Sarcopenia is also a phenomenon commonly observed in patients with LC, there has been a prevalence of 61% and 31% in men and women respectively.

Carboplatin dose that is administered to the patient is calculated by the Calvert formula, this requires the calculation of glomerular filtration rate (GFR). There are various quantified and estimated methods to calculate GFR; however the validated and most commonly used is estimated by the Cockroft-Gault formulae. It is known that due to various factors, variables required for calculation (as creatinine) could be modify the result, may became unreliable, it is why it is important to consider changes in body composition of NSCLC patients with sarcopenia.

HYPOTHESIS:

Sarcopenia participants receive a 20% more dose of Carboplatin per Free Fat Mass (kg / mg) than those without sarcopenia.

Sarcopenic patients, have more severe toxicity related to chemotherapy than those without sarcopenia.

METHODOLOGY:

NSCLC patients with advanced NSCLC (inoperable stage III or IV ) will be included.

Clinicopathological baseline of patients such as age, sex, stage, ECOG, weight, height, body composition, Subjective Global Assessment, frequency of food consumption, albumin, hemoglobin, hematocrit, glomerular filtration rate, carboplatin administered dosage, quality of life, etc.

A subsequent follow-up evaluation will be made after 1st and 2nd cycle of treatment to assess toxicity.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 132
• Est. completion date: December 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of NSCLC Stage IV (stratification according to the American Joint Committee on Cancers - 7th edition)

• Candidates for treatment with carboplatin plus paclitaxel 1st line

• Performance status (ECOG 0-2)

• Laboratory studies that demonstrate adequate renal, hepatic and hematologic function (blood chemistry and blood count)

• Normal renal ultrasound prior to initiation of treatment

Exclusion Criteria:

• Patients with renal impairment (KDOQI 3-5)

• Patients who do not have computed tomography study at baseline

• Uncontrolled blood pressure (> 140 mmHg)

• Uncontrolled diabetes (> 130 mg / dL)

• Obstruction in kidney (s) or ureter (s)

• Dehydrated patients

• Patients with high consumption of NSAIDs (aspirin, ibuprofen, etc.> 1 month)

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Sarcopenia
• Toxicity

Intervention

Drug:
• Carboplatin
Patients will receive carboplatin according to the carboplatin area under the curve dose calculation for 2 cycles to evaluate toxicity.

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Cancerologia	Mexico City

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Nacional de Cancerologia de Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (17)

Baracos VE, Reiman T, Mourtzakis M, Gioulbasanis I, Antoun S. Body composition in patients with non-small cell lung cancer: a contemporary view of cancer cachexia with the use of computed tomography image analysis. Am J Clin Nutr. 2010 Apr;91(4):1133S-1137S. doi: 10.3945/ajcn.2010.28608C. Epub 2010 Feb 17. — View Citation

Botev R, Mallie JP, Wetzels JF, Couchoud C, Schuck O. The clinician and estimation of glomerular filtration rate by creatinine-based formulas: current limitations and quo vadis. Clin J Am Soc Nephrol. 2011 Apr;6(4):937-50. doi: 10.2215/CJN.09241010. Epub 2011 Mar 31. — View Citation

Calvert AH, Newell DR, Gumbrell LA, O'Reilly S, Burnell M, Boxall FE, Siddik ZH, Judson IR, Gore ME, Wiltshaw E. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989 Nov;7(11):1748-56. doi: 10.1200/JCO.1989.7.11.1748. — View Citation

Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580. — View Citation

Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, Ferry DR, Rudd RM, Spiro SG, Cook JE, Trask C, Bessell E, Connolly CK, Tobias J, Souhami RL. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol. 1999 Oct;17(10):3188-94. doi: 10.1200/JCO.1999.17.10.3188. — View Citation

Ekhart C, Rodenhuis S, Schellens JH, Beijnen JH, Huitema AD. Carboplatin dosing in overweight and obese patients with normal renal function, does weight matter? Cancer Chemother Pharmacol. 2009 Jun;64(1):115-22. doi: 10.1007/s00280-008-0856-x. Epub 2008 Nov 7. — View Citation

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9. — View Citation

Gordon JN, Green SR, Goggin PM. Cancer cachexia. QJM. 2005 Nov;98(11):779-88. doi: 10.1093/qjmed/hci127. Epub 2005 Oct 7. — View Citation

Gronberg BH, Bremnes RM, Flotten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollali T, Wammer F, Aasebo U, Sundstrom S. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. doi: 10.1200/JCO.2008.20.9114. Epub 2009 May 11. — View Citation

Hudson JQ, Owens HM, Fleckenstein JF, Loveless VS, Krauss AG, Hak LJ. Performance of methods to assess kidney function in a predominantly overweight sample of patients with liver disease. Ren Fail. 2013;35(2):249-56. doi: 10.3109/0886022X.2012.745786. Epub 2012 Nov 26. — View Citation

Kaag D. Carboplatin dose calculation in lung cancer patients with low serum creatinine concentrations using CKD-EPI and Cockcroft-Gault with different weight descriptors. Lung Cancer. 2013 Jan;79(1):54-8. doi: 10.1016/j.lungcan.2012.10.009. Epub 2012 Nov 4. — View Citation

Muscaritoli M, Bossola M, Aversa Z, Bellantone R, Rossi Fanelli F. Prevention and treatment of cancer cachexia: new insights into an old problem. Eur J Cancer. 2006 Jan;42(1):31-41. doi: 10.1016/j.ejca.2005.07.026. Epub 2005 Nov 28. — View Citation

Nannan Panday VR, van Warmerdam LJ, Huizing MT, Ten Bokkel Huinink WW, Vermorken JB, Giaccone G, Veenhof CH, Schellens JH, Beijnen JH. Carboplatin dosage formulae can generate inaccurate predictions of Carboplatin exposure in carboplatin/paclitaxel combination regimens. Clin Drug Investig. 1998;15(4):327-35. doi: 10.2165/00044011-199815040-00009. — View Citation

Ottery FD. Cancer cachexia: prevention, early diagnosis, and management. Cancer Pract. 1994 Mar-Apr;2(2):123-31. Erratum In: Cancer Pract 1994 Jul-Aug;2(4):263. — View Citation

Ruiz-Godoy L, Rizo Rios P, Sanchez Cervantes F, Osornio-Vargas A, Garcia-Cuellar C, Meneses Garcia A. Mortality due to lung cancer in Mexico. Lung Cancer. 2007 Nov;58(2):184-90. doi: 10.1016/j.lungcan.2007.06.007. Epub 2007 Jul 30. — View Citation

Sanchez-Lara K, Turcott JG, Juarez E, Guevara P, Nunez-Valencia C, Onate-Ocana LF, Flores D, Arrieta O. Association of nutrition parameters including bioelectrical impedance and systemic inflammatory response with quality of life and prognosis in patients with advanced non-small-cell lung cancer: a prospective study. Nutr Cancer. 2012;64(4):526-34. doi: 10.1080/01635581.2012.668744. Epub 2012 Apr 10. — View Citation

Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. doi: 10.1056/NEJMoa011954. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Determine if the dose of carboplatin-based chemotherapy in patients according to the amount of fat-free mass is directly associated with toxicity	Three weeks after the application of chemotherapy to detect changes from Baseline
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Determine if the dose of carboplatin-based chemotherapy in patients according to the amount of fat-free mass is directly associated with toxicity	Six weeks after the application of chemotherapy to detect changes from Baseline
Secondary	Compare different formulas to calculate Glomerular Filtration Rate taking as gold standard cystatin c	Calculate the glomerular filtration rate given the amount of fat-free mass (MSA-eCrCl) and correlate with cystatin C and formulas as Cockroft-Gault, Levey, The Modification of Diet in Renal Disease (MDRD) and Chronic kidney disease epidemiology collaboration (CKD-EPI).	Basal evaluation