Study of Participants With Advanced Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00948675
First received: July 28, 2009
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Advanced Non-Small Cell Lung Cancer
Drug: Pemetrexed
Drug: Carboplatin
Drug: Paclitaxel
Biological: Bevacizumab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Randomization to measured progressive disease up to 39.49 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 361
Study Start Date: September 2009
Estimated Study Completion Date: January 2015
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pemetrexed + Carboplatin + Pemetrexed
Pemetrexed and Carboplatin followed by Pemetrexed
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.
Active Comparator: Paclitaxel + Carboplatin + Bevacizumab
Paclitaxel, Carboplatin, and Bevacizumab followed by Bevacizumab
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00948675

  Show 45 Study Locations
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

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00948675     History of Changes
Other Study ID Numbers: 13258, H3E-US-S130
Study First Received: July 28, 2009
Results First Received: January 14, 2014
Last Updated: March 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Advanced Non-Small Cell Lung Cancer of Nonsquamous Histology
Advanced Lung Cancer
Non-Small Cell Lung Cancer
Lung Cancer

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
Bevacizumab
Pemetrexed
Carboplatin
Paclitaxel
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014