A Study of Induction and Maintenance Treatment of Advanced Non-squamous 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:
NCT00789373
First received: November 10, 2008
Last updated: May 30, 2014
Last verified: May 2014
  Purpose

This study will compare progression-free survival in patients with advanced non-squamous non-small cell lung cancer. Patients who do not progress following 4 cycles of induction treatment with pemetrexed and cisplatin will be randomized 2:1 to receive either maintenance pemetrexed or placebo.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: Pemetrexed
Drug: Cisplatin
Drug: Placebo
Other: Best Supportive Care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance Pemetrexed Plus Best Supportive Care Versus Best Supportive Care Immediately Following Induction Treatment With Pemetrexed + Cisplatin for Advanced Non-squamous Non-Small Cell Lung Cancer.

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Investigator-assessed Objective Progression-free Survival (PFS) [ Time Frame: Date of randomization to the date of measured PD or date of death from any cause (up to 19.3 months) ] [ Designated as safety issue: Yes ]
    Investigator-assessed objective PFS was measured from the date of randomization to the first date of objectively determined progressive disease (PD) or death from any cause. For patients not known to have died as of the data cutoff date and who did not have objective PD, PFS was censored at the date of last objective tumor assessment. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD = 20% increase in sum of longest diameter of target lesions.


Secondary Outcome Measures:
  • Independently-assessed Objective Progression-free Survival (PFS) [ Time Frame: Date of randomization to first date of measured PD or date of death from any cause (up to 19.3 months) ] [ Designated as safety issue: Yes ]
    To further evaluate the robustness of the PFS analysis, Lilly established an independent review of PFS to assess the potential for investigator bias in the determination of objective PD. PFS was measured from the date of randomization to the first date of objectively determined PD or death. For patients alive as of the data cutoff date and who did not have PD, PFS was censored at the date of the last objective tumor assessment. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD = 20% increase in sum of longest diameter of target lesions.

  • Overall Survival (OS) [ Time Frame: Date of randomization to the date of death from any cause up to 39.5 months ] [ Designated as safety issue: Yes ]
    OS is the duration from enrollment to death. For patients who are alive, OS is censored at the last contact.

  • Change From Baseline in the EuroQol Instrument (EQ-5D) Index Score [ Time Frame: Baseline randomization through 30-day post-discontinuation visit (up to 19.3 months) ] [ Designated as safety issue: No ]
    The EQ-5D is a generic instrument that describes health status in 5 attributes (mobility, self-care, pain/discomfort, anxiety/depression, usual activities) using a three level scale (no problem, some problems, and major problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score range from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension).

  • Change From Baseline in EuroQol Instrument (EQ-5D) Visual Analog Scale (VAS) [ Time Frame: Baseline randomization through 30-day post-discontinuation visit (up to 19.3 months) ] [ Designated as safety issue: No ]
    Patients indicate their present health state through completion of the VAS. Possible scores range from 0 (worst imaginable health state) to 100 (best imaginable health state).

  • Percentage of Participants With Hospitalizations Due to Adverse Events or Requiring Transfusion (Resource Utilization) [ Time Frame: Baseline randomization through 30-day post-discontinuation visit (up to 19.3 months) ] [ Designated as safety issue: No ]
  • Percentage of Participants With a Non-Serious Adverse Event (AE) During Maintenance Phase [ Time Frame: Baseline randomization through 30-day post-discontinuation visit (up to 49.7 months) ] [ Designated as safety issue: Yes ]
    A summary of non-serious AEs is located in the Reported Adverse Event Module.

  • Percentage of Participants With Serious Adverse Events During Maintenance Phase [ Time Frame: Baseline randomization through 30-day post-discontinuation visit (up to 49.7 months) ] [ Designated as safety issue: Yes ]
    A summary of serious adverse events is located in the Reported Adverse Event Module.

  • Percentage of Participants With Objective Tumor Response (Response Rate) During Maintenance Phase of Study up to Primary Data Cut-Off [ Time Frame: Baseline to date of measured progressive disease (up to 19.3 months) ] [ Designated as safety issue: No ]
    Analysis for combined phases was not performed since response was calculated separately for each phase of study. Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response(PR)is at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease(PD) is at least a 20% increase in sum of longest diameter of target lesions; Stable Disease(SD)=no change or small changes that do not meet the above criteria for CR, PR, or PD.

  • Percentage of Participants With Independently-Assessed Objective Tumor Response (Response Rate) During Maintenance Phase Up to Primary Data Cut-Off [ Time Frame: Date of randomization to date of measured PD (up to 19.3 months) ] [ Designated as safety issue: No ]
    Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) is at least a 20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=no change or small changes that do not meet the above criteria for CR, PR, or PD. Response Rate = (CR+PR)/Participants in Arm*100. Disease Control Rate=(CR+PR+SD)/Number of Participants in Arm*100.


Enrollment: 939
Study Start Date: November 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: pemetrexed + cisplatin followed by pemetrexed
pemetrexed plus cisplatin followed by pemetrexed plus best supportive care
Drug: Pemetrexed
Induction therapy: 500 mg/m^2, intravenous (IV), on Day 1 of each 21-day cycle for 4 cycles
Other Names:
  • Alimta
  • LY231514
Drug: Cisplatin
Induction therapy: Cisplatin: 75 mg/m^2, IV, on Day 1 of each 21-day cycle for 4 cycles
Drug: Pemetrexed
Maintenance therapy: 500 mg/m^2, IV, on Day 1 of each 21-day cycle until progressive disease or treatment discontinuation.
Other Names:
  • Alimta
  • LY231514
Other: Best Supportive Care
Best Supportive Care is treatment given with the intent to maximize quality of life. Best Supportive Care excludes any treatment in which the goal is to cure or slow the progression of the study disease. Patients will receive Best Supportive Care as judged by their treating physician. Those therapies considered acceptable include, but are not limited to, palliative radiation to extrathoracic structures, antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, and/or nutritional support (enteral or parenteral).
Placebo Comparator: pemetrexed + cisplatin followed by placebo
pemetrexed plus cisplatin followed by placebo plus best supportive care
Drug: Pemetrexed
Induction therapy: 500 mg/m^2, intravenous (IV), on Day 1 of each 21-day cycle for 4 cycles
Other Names:
  • Alimta
  • LY231514
Drug: Cisplatin
Induction therapy: Cisplatin: 75 mg/m^2, IV, on Day 1 of each 21-day cycle for 4 cycles
Drug: Placebo
Maintenance therapy: Normal saline (0.9% sodium chloride) administered IV on Day 1 every 21-day cycle until progressive disease or treatment discontinuation
Other: Best Supportive Care
Best Supportive Care is treatment given with the intent to maximize quality of life. Best Supportive Care excludes any treatment in which the goal is to cure or slow the progression of the study disease. Patients will receive Best Supportive Care as judged by their treating physician. Those therapies considered acceptable include, but are not limited to, palliative radiation to extrathoracic structures, antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, and/or nutritional support (enteral or parenteral).

  Eligibility

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

Inclusion Criteria for the Induction Phase:

  • You must sign an informed consent document for clinical research.
  • You must have Stage IIIB or IV nonsquamous Non-Small Cell Lung Cancer.
  • You must at least be able to be physically mobile, take care of yourself, and must be up and about and able to perform light activities such as light housework or office work.
  • You are allowed to have had prior radiation therapy as long as it was not to more than 25% of the bone marrow and did not include the whole pelvis. Thoracic radiation must be completed more than 30 days before the study. You must be recovered from the toxic effects (except hair loss).
  • You must have at least 1 measurable tumor lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines or disease that can be evaluated by computed tomography (CT) Scan.
  • Your test results assessing the function of your blood forming tissue, kidneys, and liver must be satisfactory.
  • You must be 18 years of age or older.
  • Women must be sterile, postmenopausal or on contraception and men must be on contraception or sterile (e.g. post-vasectomy).

Exclusion Criteria for the Induction Phase:

  • You cannot have squamous cell and/or mixed small cell, non-small cell lung cancer
  • You cannot have received other investigational drugs within the last 30 days of entering the trial.
  • You cannot have previously completed or withdrawn from this study or any other study investigating pemetrexed.
  • You cannot have other serious on-going illnesses including active infections.
  • You cannot have a serious cardiac condition, such as a heart attack, angina, or heart disease within 6 months of entering the trial.
  • You cannot have had another form of cancer other than superficial basal cell and superficial squamous (skin) cell cancer, or carcinoma in situ of the cervix within the last 5 years. Patients with a history of low-grade (Gleason score less than or equal to 6) localized prostate cancer will be eligible even if diagnosed less than 5 years ago.
  • You cannot have known central nervous system (CNS) metastases, other than treated, stable brain metastasis.
  • You cannot be receiving nor have received any prior systemic anticancer therapy for lung cancer (including chemotherapy given after surgery in early-stage treatment).
  • You cannot have clinically significant third-space fluid collections (e.g. ascites or pleural effusions that cannot be controlled by drainage or other procedures).
  • You cannot have received a recent (within 30 days) or are receiving a yellow fever vaccination.
  • You are unable to stop taking more than 1.3 grams of aspirin on a daily basis or other non-steroidal anti-inflammatory drugs (NSAIDs).
  • You are unable or unwilling to take folic acid, injections of vitamin B12, or corticosteroids.
  • You cannot be pregnant or breastfeeding.

Inclusion criteria at Randomization for the Maintenance Phase:

  • You must at least be able to be physically mobile, take care of yourself, and must be up and about and able to perform light activities such as light housework or office work.
  • You must have documented radiographic evidence of a tumor response of complete response (CR), partial response (PR), or stable disease (SD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Tumor assessment must occur between Cycle 4 (Day 1) of induction therapy and the date of randomization. This response does not have to be confirmed in order for the patient to be randomized to the maintenance phase.
  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: NCT00789373

  Show 69 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 by Eli Lilly and Company

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

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00789373     History of Changes
Other Study ID Numbers: 12560, H3E-EW-S124, CTRI/2009/091/000113
Study First Received: November 10, 2008
Results First Received: June 20, 2011
Last Updated: May 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Pemetrexed
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on August 25, 2014