Chemotherapy With Pemetrexed in Combination With Platinum for Advanced Non-Small Cell Lung Cancer (NSCLC)

• ClinicalTrials.gov Identifier: NCT00402051
• Recruitment Status: Completed
• First Posted: November 22, 2006
• Results First Posted: January 7, 2010
• Last Update Posted: February 17, 2010
• Sponsor: Eli Lilly and Company
• Information provided by: Eli Lilly and Company

Study Description

Brief Summary:

This is a two-arm, parallel, open-label, Phase 2 multicenter study of pemetrexed as first line combination therapy with either cisplatin or carboplatin in the palliative setting of stage IIIb and IV non-small cell lung cancer patients. Approximately 130 patients will be included in about 15 centers in Germany and randomized to one of the above treatment regimens in a 1:1 ratio. Chemotherapy will be administered over a maximum of six cycles with a standard length of 21 days. Primary objective will be the Progression Free Survival Time of patients as assessed in both treatment arms.

Condition or disease	Intervention/treatment	Phase
Non-Small-Cell Lung Cancer	Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 133 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Phase 2 Study of Pemetrexed in Combination With Cisplatin or Carboplatin in the First Line Therapy of Advanced NSCLC
• Study Start Date: November 2006
• Actual Primary Completion Date: December 2008
• Actual Study Completion Date: May 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pemetrexed + Cisplatin	Drug: Pemetrexed; 500 mg/m2, intravenous (IV), every 21 days x 6 cycles; Other Names: LY231514; Alimta; Drug: Cisplatin; 75 mg/m2, intravenous (IV), every 21 days x 6 cycles
Experimental: Pemetrexed + Carboplatin	Drug: Pemetrexed; 500 mg/m2, intravenous (IV), every 21 days x 6 cycles; Other Names: LY231514; Alimta; Drug: Carboplatin; Area under the concentration curve (AUC) 5, intravenous (IV), every 21 days x 6 cycles

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Surviving Progression-Free at 6 Months (Progression Free Survival [PFS] Rate) [ Time Frame: Randomization to Month 6 ]
   For this study, we used the exponential distribution (assumption done for the calculation of the sample size) to estimate the PFS rate. The PFS rate (%) and the 95% confidence intervals were calculated based on the following formula: exp(-6 λ) ± 1.96 * exp(-6 λ) * (-6 λ)/√r. Where λ was calculated based on the Maximum-Likelihood estimator for ln(λ) as given by (Collett 2003): ln(λ) = ln[ r / ∑ti ] with r = number of patients with events up to 6 months, ti = survival time of patient i (i=1,…,n), event or censored up to 6 months, and n= total number of patients per treatment group.

Secondary Outcome Measures :

1. Overall Survival [ Time Frame: Randomization to date of death from any cause (up to 1 year) ]
   Defined as the time from randomization to the date of death from any cause.
2. Number of Participants With Tumor Response (as Basis for Response Rate) [ Time Frame: Every 6 weeks for 6 months during the treatment period, and every 3 months during the follow-up period, until disease progression ]
   Best overall response was evaluated using RECIST Criteria which define when cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progression") during treatment. CR: complete response, disappearance of all target lesions; PR: partial response, 30% decrease in sum of the longest diameter of target lesions; PD: progressive disease, 20% increase in sum of the longest diameter of target lesions; SD: stable disease, small changes not meeting above criteria. Response Rate: number of participants with response(CR+PR)per total population, multiplied by 100 to give a percentage.
3. Time to Treatment Failure (TTF) [ Time Frame: Randomization to stopping of treatment, progression, death or initiation of further chemotherapy, whichever occurs first (up to 1 year) ]
   Defined as time from randomization to the first date of disease progression, death due to any cause, or early discontinuation of treatment (any reason), whichever occurred first
4. Pharmacology Toxicities [ Time Frame: Every 21-day cycle for up to 6 cycles ]
   Number of patients experiencing Grade 3 or 4 hematologic and non-hematologic adverse events (AEs) possibly related to study drug or protocol procedures in this study (a subset of those listed in the AE Module). AEs were graded using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) for defining and grading specific adverse events. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death). Grade 3 AEs are severe and undesirable; Grade 4 AEs are life-threatening or disabling.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Cytologically and/or histologically confirmed NSCLC Stage IIIb or IV
• No previous systemic chemotherapy for this cancer
• At least one uni-dimensionally measurable lesion meeting Response Evaluation Criteria In Solid Tumors (RECIST) criteria
• Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1 and adequate organ function
• Prior radiation therapy allowed but limited to <25% of the patient's bone marrow

Exclusion Criteria:

• Serious concomitant systemic disorder or active infection
• Mild to moderate renal insufficiency, but unable to interrupt salicylates or other nonsteroidal anti-inflammatory drugs
• Symptomatic central nervous system (CNS) metastases requiring concurrent corticosteroid therapy
• Presence of clinically significant third-space fluid collections

Contacts and Locations

Locations

Germany

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Coswig, Germany, D-01640

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Frankfurt, Germany, 65929

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Großhansdorf, Germany, D-22927

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Halle, Germany, D-06120

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Hamburg, Germany, D-21075

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Hofheim, Germany, D-65719

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Homburg/Saar, Germany, 66421

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Immenhausen, Germany, D-34376

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Leipzig, Germany, 04207

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Luebeck, Germany, 23538

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Mainz, Germany, 55131

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Muenchen, Germany, 81664

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLilly (1-877-285-4559) or 1-317-615-4559 Mon -Fri 9 AM - 5 PM Eastern time (UTC/GMT -5 hours EST); Eli Lilly and Company

More Information

Additional Information:

Lilly Clinical Trial Registry 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schuette WH, Gröschel A, Sebastian M, Andreas S, Müller T, Schneller F, Guetz S, Eschbach C, Bohnet S, Leschinger MI, Reck M. A randomized phase II study of pemetrexed in combination with cisplatin or carboplatin as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer. Clin Lung Cancer. 2013 May;14(3):215-23. doi: 10.1016/j.cllc.2012.10.001. Epub 2013 Jan 16.

• Responsible Party: Chief Medical Officer, Eli Lilly
• ClinicalTrials.gov Identifier: NCT00402051
• Other Study ID Numbers: 11077; H3E-SB-S109 ( Other Identifier: Eli Lilly and Company )
• First Posted: November 22, 2006
• Results First Posted: January 7, 2010
• Last Update Posted: February 17, 2010
• Last Verified: February 2010

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Cisplatin; Carboplatin; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors