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Study of Participants With Advanced Non-Small Cell Lung Cancer

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ClinicalTrials.gov Identifier: NCT00948675
Recruitment Status : Completed
First Posted : July 29, 2009
Results First Posted : April 2, 2014
Last Update Posted : February 12, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE July 28, 2009
First Posted Date  ICMJE July 29, 2009
Results First Submitted Date  ICMJE January 14, 2014
Results First Posted Date  ICMJE April 2, 2014
Last Update Posted Date February 12, 2021
Actual Study Start Date  ICMJE September 1, 2009
Actual Primary Completion Date January 31, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 4, 2014)
Progression Free Survival Without Grade 4 Toxicity (G4PFS) as Measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [ Time Frame: Randomization to measured progressive disease or treatment discontinuation up to 39.49 months ]
G4PFS was defined as the duration from the date of randomization to the earliest occurrence date of one of the following three events: Common Terminology Criteria (CTC) grade 4 adverse events (G4AEs), or progressive disease (PD) or death from any cause, whichever occurred earlier. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who had no G4AEs, or PD, or death at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy.
Original Primary Outcome Measures  ICMJE
 (submitted: July 28, 2009)
Progression free survival without grade 4 toxicity as measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. [ Time Frame: Baseline to measured progressive disease or treatment discontinuation, assessed at 3 years. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2014)
  • Progression Free Survival (PFS) [ Time Frame: Randomization to measured progressive disease up to 39.49 months ]
    PFS was defined as the duration from the date of randomization to the date of progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who had no PD or death at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy.
  • Overall Survival (OS) [ Time Frame: Randomization to date of death from any cause up to 39.49 months ]
    OS is defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the last date the participant was known to be alive.
  • Percentage of Participants With Complete Response or Partial Response (Overall Tumor Response Rate) [ Time Frame: Baseline to date of objective progressive disease up to 39.49 months ]
    Overall Response rate (ORR) is the percentage of participants with a confirmed complete response (CR) or partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. ORR is calculated as a total number of participants with CR or PR from the start of study treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100.
  • Disease Control Rates Defined as Complete Response (CR), Partial Response (PR), and Stable Disease (SD) [ Time Frame: Baseline to date of objective progressive disease up to 39.49 months ]
    Disease control rate is the percentage of participants with a confirmed CR, PR or SD, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions; PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion; SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Disease control rate is calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2009)
  • Progression free survival [ Time Frame: Baseline to measured progressive disease, assessed at 3 years. ]
  • Overall survival [ Time Frame: Baseline to date of death from any cause, assessed at 3 years. ]
  • Overall Tumor Response rate [ Time Frame: Baseline to date of confirmed response, assessed at every other 21 day cycle. ]
  • Disease control rates defined as complete response, partial response, and stable disease [ Time Frame: Baseline to date of confirmed response, assessed at every other 21 day cycle. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Participants With Advanced Non-Small Cell Lung Cancer
Official Title  ICMJE A Study of Pemetrexed Plus Carboplatin Followed by Maintenance Pemetrexed vs Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Advanced NCSLC of Nonsquamous Histology
Brief Summary The purpose of this study is to compare the regimens of pemetrexed, carboplatin with pemetrexed maintenance and paclitaxel, carboplatin, bevacizumab with bevacizumab maintenance in participants with Stage IV nonsquamous non-small cell lung cancer.
Detailed Description This is a multicenter, randomized, open-label, Phase III trial. Eligible participants will be randomized in a 1:1 ratio to receive pemetrexed and carboplatin followed by pemetrexed or paclitaxel, carboplatin, and bevacizumab followed by bevacizumab as their study treatment. Participants randomized to Pemetrexed + Carboplatin + Pemetrexed will receive folic acid, vitamin B12, and dexamethasone as stated in the pemetrexed label. Before administration of paclitaxel, participants randomized to Paclitaxel + Carboplatin + Bevacizumab will receive premedication (dexamethasone, diphenhydramine, and cimetidine or ranitidine) as recommended in the paclitaxel label.
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
Condition  ICMJE Advanced Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Pemetrexed
    Induction therapy: 500 milligrams/square meter (mg/m²) given intravenously every 21 days for 4 cycles. Maintenance therapy: 500 mg/m² given intravenously every 21 days until disease progression or treatment discontinuation.
    Other Name: ALIMTA, LY231514
  • Drug: Carboplatin
    Induction Therapy (every 21 days for 4 cycles): Area Under the Curve (AUC) 6 [maximum possible dose of 900 milligrams (mg)] intravenously infused over 30 minutes.
  • Drug: Paclitaxel
    Induction Therapy (every 21 days for 4 cycles): 200 mg/m² intravenously infused over 3 hours
  • Biological: Bevacizumab
    Induction therapy: 15 milligrams/kilogram (mg/kg) given intravenously every 21 days for 4 cycles. Maintenance therapy: 15 mg/kg given intravenously every 21 days until disease progression or treatment discontinuation.
Study Arms  ICMJE
  • Experimental: Pemetrexed + Carboplatin + Pemetrexed
    Pemetrexed and Carboplatin followed by Pemetrexed
    Interventions:
    • Drug: Pemetrexed
    • Drug: Carboplatin
  • Active Comparator: Paclitaxel + Carboplatin + Bevacizumab
    Paclitaxel, Carboplatin, and Bevacizumab followed by Bevacizumab
    Interventions:
    • Drug: Carboplatin
    • Drug: Paclitaxel
    • Biological: Bevacizumab
Publications * Zinner RG, Obasaju CK, Spigel DR, Weaver RW, Beck JT, Waterhouse DM, Modiano MR, Hrinczenko B, Nikolinakos PG, Liu J, Koustenis AG, Winfree KB, Melemed SA, Guba SC, Ortuzar WI, Desaiah D, Treat JA, Govindan R, Ross HJ. PRONOUNCE: randomized, open-label, phase III study of first-line pemetrexed + carboplatin followed by maintenance pemetrexed versus paclitaxel + carboplatin + bevacizumab followed by maintenance bevacizumab in patients ith advanced nonsquamous non-small-cell lung cancer. J Thorac Oncol. 2015 Jan;10(1):134-42. doi: 10.1097/JTO.0000000000000366.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 4, 2014)
361
Original Estimated Enrollment  ICMJE
 (submitted: July 28, 2009)
360
Actual Study Completion Date  ICMJE November 6, 2020
Actual Primary Completion Date January 31, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • a histologic or cytologic diagnosis of advanced non-small cell lung cancer (NSCLC) [Stage IV from the American Joint Committee on Cancer Staging Criteria (AJCC) staging system, version 7.0, including both M1a and M1b], other than predominantly squamous cell histology, that is not amenable to curative therapy. Participants may not have received any prior systemic chemotherapy, immunotherapy, targeted therapy, or biological therapy, including adjuvant therapy, for any stage of NSCLC.
  • prior radiation therapy is allowed to < 25% of the bone marrow; however, prior radiation to the whole pelvis not allowed.
  • good performance status.
  • adequate organ function.
  • estimated life expectancy of at least 12 weeks.

Exclusion Criteria:

  • known central nervous system (CNS) disease, other than treated brain metastasis.
  • major surgical procedure, open biopsy, open pleurodesis, or significant traumatic injury within 28 days prior to study or have an anticipated need for major surgery during the study.
  • core biopsy or other minor surgical procedure, excluding placement of vascular access device, closed pleurodesis, thoracentesis, and mediastinoscopy, within 7 days prior to study.
  • history of gastrointestinal fistula, perforation, or abscess, inflammatory bowel disease, or diverticulitis.
  • currently receiving ongoing treatment with full-dose warfarin or equivalent
  • significant vascular disease within 6 months prior to Day 1 of Cycle 1.
  • evidence of bleeding diathesis or coagulopathy.
  • serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the participant's ability to adhere to the protocol.
  • serious cardiac condition, such as myocardial infarction, angina, or heart disease.
  • inadequately controlled hypertension.
  • any prior history of hypertensive crisis or hypertensive encephalopathy.
  • serious, nonhealing wound, active ulcer, or untreated bone fracture.
  • another active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within the last 5 years.
  • previously received treatment with paclitaxel, carboplatin, pemetrexed, or bevacizumab (prior intravitreal administration of bevacizumab does not preclude study participation).
  • pregnant or breast-feeding.
  • history of stroke or transient ischemic attack within 6 months prior to study.
  • known sensitivity to any component of paclitaxel, carboplatin, pemetrexed, or bevacizumab.
  • history of hemoptysis within 3 months prior to randomization.
  • unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs).
  • unwilling to take folic acid or vitamin B12 supplementation.
  • clinically significant third-space fluid collections, for example, ascites or pleural effusions that cannot be controlled by drainage. Participants with M1a disease with pleural effusions are eligible if the effusions can be adequately controlled.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
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 United States
Removed Location Countries Puerto Rico
 
Administrative Information
NCT Number  ICMJE NCT00948675
Other Study ID Numbers  ICMJE 13258
H3E-US-S130 ( Other Identifier: Eli Lilly and Company )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP