Alimta® Versus Its Combination With Carboplatin in Advanced Non-small-cell Lung Cancer in Patients Performance Status 2

NCT01836575 | Completed Phase 3 DMC

• 3 other identifiers: H3E-BL-O027-PS2H3E - US -I023INCA-Lung001
• Study Type: interventional
• Target: 228
• Locations: 2 countries
• Sites: 9

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.

Conditions

Non Small Cell Lung Carcinoma

Keywords

Advanced NSCLC; PS2; Pemetrexed; First line; non squamous

Outcome Measures

Primary Outcomes (1)

• Overall survival

  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.

  From ICF signature date until e until death date for any cause

Secondary Outcomes (3)

• Safety evaluation

  Serious Adverse Event every 6 months

• Progression free survival

  Final data analysis: Sep/2012

• Response Rate

  Final data analysis: Sep/2012

Study Arms (2)

Arm B

EXPERIMENTAL

Pemetrexed, 500mg/m2 + appropriate vitamin supplementation + Carboplatin \[Target AUC 5 IV infusion,based on Calvert formula,GFR estimated using estimated creatinine clearance per Cockcroft and Gault formula, obtained prior to each cycle\] + Antiemetic therapy at investigator's discretion.

Drug: Pemetrexed; Drug: Carboplatin

Arm A:

ACTIVE COMPARATOR

Pemetrexed, 500mg/m2 + appropriate vitamin supplementation + Antiemetic therapy at investigator's discretion.

Drug: Pemetrexed

Interventions

Pemetrexed DRUG

Pemetrexed, 500 mg/m2 + Pretreatment \[dexamethasone + vitamin B12 + folic acid, as per pemetrexed label\] + Antiemetic therapy at investigator's discretion.

Also known as: Arm A - active comparator Pemetrexed (Alimta).

Arm A:; Arm B

Carboplatin DRUG

Carboplatin \[Target AUC 5 IV infusion,based on Calvert formula,GFR estimated using estimated creatinine clearance per Cockcroft and Gault formula, obtained prior to each cycle\].

Also known as: Carboplatin AUC 5 IV in 5% dextrose or 0.9% sodium chloride.

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed NSCLC in stage IIIB (with a cytologically positive pleural or pericardial effusion) or stage IV, according to the sixth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual37;
• Age \> 18 years;
• No prior chemotherapy, including adjuvant or neoadjuvant therapy, for the treatment of NSCLC;
• Histological confirmation of any non-squamous histological type of NSCLC, given the recent findings of treatment benefit in this population44;
• ECOG performance status of 2;
• At least 3 weeks must have elapsed since major surgery, and at least 1 week since mediastinoscopy, pleuroscopy, or thoracostomy;
• Patients must have measurable disease, defined as lesions that can be accurately measured in at least 1 dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques (computed tomography \[CT\] or magnetic resonance imaging \[MRI\] scan) or as ≥ 10 mm with spiral CT scan;
• Adequate organ function as indicated by the following:
• White blood cell (WBC) count ≥ 3500/mm3
• Absolute neutrophil count (ANC) ≥1500/mm3
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 100,000/ mm3
• Total bilirubin ≤ 2 times the upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the ULN, unless liver metastases present, in which case AST and ALT have to be ≤ 5 times the ULN
• Estimated glomerular filtration rate (GFR) ≥ 45 mL/min

You may not qualify if:

• ECOG performance status other than 2;
• Prior chemotherapy for the treatment of NSCLC;
• Lesions that have been irradiated cannot be included as sites of measurable disease. If the only measurable lesion was previously irradiated the patient cannot be included;
• Symptomatic central nervous system (CNS) metastases. Prior CNS metastases are allowed if the patient is neurologically stable and not receiving corticosteroids;
• Serious uncontrolled intercurrent medical or psychiatric illness;
• Active and ongoing systemic infection;
• Second primary malignancy (except in situ carcinoma of the cervix, in situ carcinoma of the bladder, adequately treated basal-cell carcinoma of the skin, adequately treated squamous-cell carcinoma of the skin, T1 vocal cord cancer in remission, or prior malignancy treated more than 5 years prior to enrollment and without recurrence);
• Known hypersensitivity to pemetrexed;
• known hypersensitivity to carboplatin;
• Pregnancy or lactation;
• Use of any investigational agent within 30 days prior to enrollment into the study;
• Unable to discontinue administration of non-steroidal anti-inflammatory (NSAIDSs) agents for 2 days before, the day of and 2 days after the dose of pemetrexed, in the case of NSAIDs with short half-life, such as ibuprofen (total of 5 days), in patients with a GFR between 45 and 79 mL/min; and for 5 days before, the day of and 2 days after the dose of pemetrexed, in the case of NSAIDs with long half-life (total of 8 days, see 7.4.2) in all patients; patients with a GFR ≥ 80 mL/min may receive concomitant study treatment and ibuprofen or aspirin (≤ 1.3 g/day);
• Inability to comply with requirements and procedures of study.

Sponsors & Collaborators

• Instituto Nacional de Cancer, Brazil: lead
• Eli Lilly and Company: collaborator

Study Sites (9)

The Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Instituto do Câncer do Ceará - ICC

Fortaleza, Ceará, Brazil

Location

Hospital Lifecenter

Belo Horizonte, Minas Gerais, Brazil

Location

INCA

Rio de Janeiro, Rio de Janeiro, Brazil

Location

Hospital Caridade de Ijuí - CACON

Ijuí, Rio Grande do Sul, Brazil

Location

Hospital São Lucas

Porto Alegre, Rio Grande do Sul, Brazil

Location

Centro de Pesquisas Oncológicas - CEPON

Florianópolis, Santa Catarina, Brazil

Location

Hospital Amaral Carvalho

Jaú, São Paulo, Brazil

Location

Instituto do Câncer Arnaldo Vieira de Carvalho

São Paulo, São Paulo, Brazil

Location

Related Publications (2)

• Gijtenbeek RG, de Jong K, Venmans BJ, van Vollenhoven FH, Ten Brinke A, Van der Wekken AJ, van Geffen WH. Best first-line therapy for people with advanced non-small cell lung cancer, performance status 2 without a targetable mutation or with an unknown mutation status. Cochrane Database Syst Rev. 2023 Jul 7;7(7):CD013382. doi: 10.1002/14651858.CD013382.pub2.

  PMID: 37419867 DERIVED

• 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.

  PMID: 23775961 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; Carboplatin; Glucose; Sodium Chloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Hexoses; Monosaccharides; Sugars; Carbohydrates; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Carlos G Ferreira, PhD

  National Cancer Institute, France

  PRINCIPAL INVESTIGATOR

• Rogerio Lilenbaum, MD

  The Mount Sinai Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Carlos Henrique E Barrios, MD

  Pontifícia Universidade Católica do RS

  PRINCIPAL INVESTIGATOR

• Carlos Augusto M. Beato, MD

  Hospital Amaral Carvalho

  PRINCIPAL INVESTIGATOR

• José Rodrigues, MD

  Instituto do Câncer Arnaldo Vieira Carvalho - ICAVC

  PRINCIPAL INVESTIGATOR

• Yeni Neron, MD

  Centro de Pesquisas Oncológicas - CEPON

  PRINCIPAL INVESTIGATOR

• André Murad, PhD

  Lifecenter Hospital

  PRINCIPAL INVESTIGATOR

• Ronaldo A Ribeiro, PhD

  Instituto do Câncer do Ceará - ICC

  PRINCIPAL INVESTIGATOR

• Fábio Franke, MD

  Hospital de Caridade de Ijuí - CACON

  PRINCIPAL INVESTIGATOR

• Mauro Zukin, MD

  National Cancer Institute, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2010
• First Posted: April 22, 2013
• Study Start: April 1, 2008
• Primary Completion: January 1, 2012
• Study Completion: December 1, 2012
• Last Updated: April 22, 2013

Record last verified: 2013-04

Locations

US (1); BR (8)