Alimta® Versus Its Combination With Carboplatin in Advanced Non-small-cell Lung Cancer in Patients Performance Status 2 (PS2)
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ClinicalTrials.gov Identifier: NCT01836575 |
Recruitment Status :
Completed
First Posted : April 22, 2013
Last Update Posted : April 22, 2013
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Tracking Information | |||||||||||||||||||||||||||||||
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First Submitted Date ICMJE | December 30, 2010 | ||||||||||||||||||||||||||||||
First Posted Date ICMJE | April 22, 2013 | ||||||||||||||||||||||||||||||
Last Update Posted Date | April 22, 2013 | ||||||||||||||||||||||||||||||
Study Start Date ICMJE | April 2008 | ||||||||||||||||||||||||||||||
Actual Primary Completion Date | January 2012 (Final data collection date for primary outcome measure) | ||||||||||||||||||||||||||||||
Current Primary Outcome Measures ICMJE |
Overall survival [ Time Frame: From ICF signature date until e until death date for any cause ] Each patient will be followed from inclusion date in the study (ICF signature) until the death date for any cause, whichever came first, assessed up to one year after completion of study treatment. Primary objective of this study is to determine and compare the overall survival produced by pemetrexed as a single-agent and by the combination of pemetrexed plus carboplatin in a patient with previously untreated, advanced non-squamous NSCLC and an ECOG Performance status of 2.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||||||||||||||||||||||||||
Change History | No Changes Posted | ||||||||||||||||||||||||||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||||||||||||||||||||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||||||||||||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||||||||||||||||||||||||
Descriptive Information | |||||||||||||||||||||||||||||||
Brief Title ICMJE | Alimta® Versus Its Combination With Carboplatin in Advanced Non-small-cell Lung Cancer in Patients Performance Status 2 | ||||||||||||||||||||||||||||||
Official Title ICMJE | Phase III Trial of Single-Agent Pemetrexed (Alimta®) Versus the Combination of Carboplatin and Pemetrexed in Patients With Advanced Non-small-cell Lung Cancer and Performance Status of 2 | ||||||||||||||||||||||||||||||
Brief Summary | Optimal management of patients with advanced NSCLC and with PS 2 remains controversial and underrepresented in clinical trials, typically accounting for 5 to 10% of enrolled patients. Patient PS 2 proportion in population-based studies is considerably higher than that included in clinical trials. Management of patients with PS of 2 in clinical practice is empirical and inconsistent. Patients have median overall survival of 3 to 5 months in randomized trials, and treatment options include best supportive care, single-agent and combination chemotherapy. Retrospective studies have suggested that patients PS 2 may benefit from first-line chemotherapy in terms of symptom improvement and overall survival. In many of these studies, single-agent chemotherapy was compared with best supportive care alone. Data on the role of cisplatin-based combinations for patients with PS 2 is more scant, with one study questioning its benefit, and another interrupting accrual because of undue toxicity. With regards to carboplatin, the Cancer and Leukemia Group B (CALGB) study 9730 compared paclitaxel plus carboplatin versus paclitaxel alone in a subgroup of 107 patients with PS 2; the median overall survival was significantly longer in group treated with combination chemotherapy (4.7 versus 2.4 months). Combination chemotherapy with carboplatin and paclitaxel also produced a statistically significantly higher incidence of severe hematological and non-hematological toxicities. On the basis of aforementioned results, a recent European panel stated that carboplatin-based or low-dose cisplatin-based doublets might represent alternative options to single-agent chemoterapy in patients PS 2. Outside clinical trials, single-agent chemotherapy with a 3rd generation agent remains valid option for patients PS2. Results demonstrate that pemetrexed is an agent with established single-agent activity in NSCLC, and suggest it is a potential candidate for combinations with platinum and other agents currently utilized for patients with advanced NSCLC. Favorable toxicity profile of pemetrexed suggests that this agent is an ideal candidate for single agent testing and in combination among patients with PS 2. Substantial doubt remains in the comparative benefit from monotherapy versus combination. Starting dose and schedule of pemetrexed were set for this study based on its current labeling in the 2nd line treatment of metastatic NSCLC and 1st line treatment of malignant pleural mesothelioma. | ||||||||||||||||||||||||||||||
Detailed Description | This is a Phase III, open label, randomized study to enroll 228 patients with advanced in a 1:1 ratio at the time of registration. Patients in Arm A will receive pemetrexed, 500 mg/m2, with appropriate vitamin supplementation; patients in Arm B will receive the same dose and schedule of pemetrexed as in Arm A, in combination with carboplatin, AUC of 5. For the purpose of the study, treatment (Arm A or Arm B) will consist of up to four cycles of therapy (repeated every 21 days). Primary endpoint of the study is overall survival; secondary endpoints include toxicity, response rate, and progression-free survival. At the time of analysis, patients will be stratified according to age (≥ 70 versus < 70 years), disease stage (IIIB versus IV), site, and weight loss (≥ 5 Kg versus < 5 Kg). The dose of carboplatin will be determined according to the formula developed by Calvert et al., which is shown in equation [1] below and uses the estimated creatinine clearance according to the method of Cockcroft and Gault for estimation of the glomerular filtration rate (GFR) (equation [2] below):
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Study Type ICMJE | Interventional | ||||||||||||||||||||||||||||||
Study Phase ICMJE | Phase 3 | ||||||||||||||||||||||||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Non Small Cell Lung Carcinoma | ||||||||||||||||||||||||||||||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Zukin M, Barrios CH, Pereira JR, Ribeiro Rde A, Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, Araujo LH, Baldotto CS, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. doi: 10.1200/JCO.2012.48.1911. Epub 2013 Jun 17. | ||||||||||||||||||||||||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||||||||||||||||||||||||||
Recruitment Status ICMJE | Completed | ||||||||||||||||||||||||||||||
Actual Enrollment ICMJE |
228 | ||||||||||||||||||||||||||||||
Original Actual Enrollment ICMJE | Same as current | ||||||||||||||||||||||||||||||
Actual Study Completion Date ICMJE | December 2012 | ||||||||||||||||||||||||||||||
Actual Primary Completion Date | January 2012 (Final data collection date for primary outcome measure) | ||||||||||||||||||||||||||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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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 | Brazil, United States | ||||||||||||||||||||||||||||||
Removed Location Countries | |||||||||||||||||||||||||||||||
Administrative Information | |||||||||||||||||||||||||||||||
NCT Number ICMJE | NCT01836575 | ||||||||||||||||||||||||||||||
Other Study ID Numbers ICMJE | H3E-BL-O027-PS2 H3E - US -I023 ( Other Identifier: INCA-Lung001 ) INCA-Lung001 ( Other Identifier: INCA - Brazilian National Cancer Institute ) |
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Has Data Monitoring Committee | Yes | ||||||||||||||||||||||||||||||
U.S. FDA-regulated Product | Not Provided | ||||||||||||||||||||||||||||||
IPD Sharing Statement ICMJE | Not Provided | ||||||||||||||||||||||||||||||
Current Responsible Party | Instituto Nacional de Cancer, Brazil | ||||||||||||||||||||||||||||||
Original Responsible Party | Same as current | ||||||||||||||||||||||||||||||
Current Study Sponsor ICMJE | Instituto Nacional de Cancer, Brazil | ||||||||||||||||||||||||||||||
Original Study Sponsor ICMJE | Same as current | ||||||||||||||||||||||||||||||
Collaborators ICMJE | Eli Lilly and Company | ||||||||||||||||||||||||||||||
Investigators ICMJE |
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PRS Account | Instituto Nacional de Cancer, Brazil | ||||||||||||||||||||||||||||||
Verification Date | April 2013 | ||||||||||||||||||||||||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |